Publications (24)114.88 Total impact
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Article: Diagnosis of Lung Cancer in Small Biopsies and Cytology: Implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification.
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ABSTRACT: The new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification provides, for the first time, standardized terminology for lung cancer diagnosis in small biopsies and cytology; this was not primarily addressed by previous World Health Organization classifications. Until recently there have been no therapeutic implications to further classification of NSCLC, so little attention has been given to the distinction of adenocarcinoma and squamous cell carcinoma in small tissue samples. This situation has changed dramatically in recent years with the discovery of several therapeutic options that are available only to patients with adenocarcinoma or NSCLC, not otherwise specified, rather than squamous cell carcinoma. This includes recommendation for use of special stains as an aid to diagnosis, particularly in the setting of poorly differentiated tumors that do not show clear differentiation by routine light microscopy. A limited diagnostic workup is recommended to preserve as much tissue for molecular testing as possible. Most tumors can be classified using a single adenocarcinoma marker (eg, thyroid transcription factor 1 or mucin) and a single squamous marker (eg, p40 or p63). Carcinomas lacking clear differentiation by morphology and special stains are classified as NSCLC, not otherwise specified. Not otherwise specified carcinomas that stain with adenocarcinoma markers are classified as NSCLC, favor adenocarcinoma, and tumors that stain only with squamous markers are classified as NSCLC, favor squamous cell carcinoma. The need for every institution to develop a multidisciplinary tissue management strategy to obtain these small specimens and process them, not only for diagnosis but also for molecular testing and evaluation of markers of resistance to therapy, is emphasized.Archives of pathology & laboratory medicine 09/2012; · 2.58 Impact Factor -
Article: 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.
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ABSTRACT: 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.Archives of pathology & laboratory medicine 08/2012; · 2.58 Impact Factor -
Article: High-resolution computed tomography screening for lung cancer: unexpected findings and new controversies regarding adenocarcinogenesis.
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ABSTRACT: Recent advances in human imaging technologies reawakened interest in lung cancer screening. Although historic and current preliminary and noncontrolled studies have not shown a decrease in lung cancer mortality in screened populations, many explanations have been proffered while the lung cancer community awaits the results of several large controlled population studies. To critically review the current model of adenocarcinoma development against the background of lung cancer screening results combined with observational pathologic and radiographic studies. Published articles pertaining to lung cancer screening, lung adenocarcinoma pathology, and radiology accessible through PubMed form the basis for this review. The current adenocarcinogenesis model is probably valid for many but not all lung adenocarcinomas. Screening data combined with radiographic and pathologic studies suggest that not all lung adenocarcinomas are clinically aggressive, and it is uncertain whether all aggressive adenocarcinomas arise from identified precursors.Archives of pathology & laboratory medicine 01/2010; 134(1):41-8. · 2.58 Impact Factor -
Article: Population-based trends in lung cancer incidence in women.
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ABSTRACT: Lung cancer is the leading cause of cancer mortality in women worldwide. Although the rise and growing epidemic status of lung cancer are overwhelmingly attributed to tobacco use, its rank in nonsmokers as the seventh most common cause of cancer worldwide suggests that other factors contribute to this disease. The majority of lung cancers among nonsmokers occur in women. Aside from geographic, cultural, and genetic differences, hormonal and possibly infectious factors also may play etiologic roles. This review aims to discuss the epidemiology of lung cancer in women, as well as the incidence of second primaries, and presents current opinions on the myriad of causes.Seminars in Oncology 12/2009; 36(6):506-15. · 3.50 Impact Factor -
Article: Adenovirus-based vaccine prevents pneumonia in ferrets challenged with the SARS coronavirus and stimulates robust immune responses in macaques.
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ABSTRACT: A ferret model of severe acute respiratory syndrome (SARS)-CoV infection was used to evaluate the efficacy of an adenovirus vaccine. Animals were subjected to heterologous prime-boost using vectors from human serotype 5 and chimpanzee derived adenoviruses (human AdHu5 and chimpanzee AdC7) expressing spike protein followed by intranasal challenge with SARS-CoV. Vaccination led to a substantial reduction in viral load and prevented the severe pneumonia seen in unvaccinated animals. The same prime-boost strategy was effective in rhesus macaques in eliciting SARS-CoV specific immune responses. These data indicate that a heterologous adenovirus-based prime-boost vaccine strategy could safely stimulate strong immunity that may be needed for complete protection against SARS-CoV infection.Vaccine 08/2007; 25(28):5220-31. · 3.77 Impact Factor -
Article: Commonly encountered difficulties in pathologic staging of lung cancer.
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ABSTRACT: 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.Archives of pathology & laboratory medicine 08/2007; 131(7):1016-26. · 2.58 Impact Factor -
Article: Comparison of pathologic findings of baseline and annual repeat cancers diagnosed on CT screening.
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ABSTRACT: 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 06/2007; 56(2):193-9. · 3.43 Impact Factor -
Article: Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria.
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ABSTRACT: 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.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 12/2006; 1(9 Suppl):S13-9. · 4.55 Impact Factor -
Article: Bronchioloalveolar Carcinoma and Lung Adenocarcinoma: The Clinical Importance and Research Relevance of the 2004 World Health Organization Pathologic Criteria
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ABSTRACT: Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.Journal of Thoracic Oncology 10/2006; 1(9):S13-S19. · 3.66 Impact Factor -
Article: An unusual case of granulomatous lung disease. A clinical pathology conference held by the Department of Rheumatology at Hospital for Special Surgery.
HSS Journal 10/2006; 2(2):191-7. -
Article: Pathologic findings of lung tumors diagnosed on baseline CT screening.
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ABSTRACT: 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.American Journal of Surgical Pathology 06/2006; 30(5):606-13. · 4.35 Impact Factor -
Article: Tumor size is a determinant of stage distribution in t1 non-small cell lung cancer.
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ABSTRACT: 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 (< or = 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 < or = 3 cm. All clinical and pathologic characteristics were recorded. Univariate associations between nodal status and other prognostic factors were explored by chi2 and t tests. The independent effect of tumor size > 2 cm vs < or = 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 (< or = 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 (< or = 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 < or = 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.Chest 10/2005; 128(4):2304-8. · 5.25 Impact Factor -
Article: No evidence for tumorigenesis of AAV vectors in a large-scale study in mice.
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ABSTRACT: 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.Molecular Therapy 09/2005; 12(2):299-306. · 6.87 Impact Factor -
Article: Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma.
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ABSTRACT: To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC). A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC. Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of "minimally invasive" BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens. There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.Journal of Clinical Oncology 06/2005; 23(14):3279-87. · 18.37 Impact Factor -
Article: Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.
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ABSTRACT: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.Clinical Cancer Research 02/2005; 11(1):232-41. · 7.74 Impact Factor -
Article: Nonspecific interstitial pneumonia: a provisional category of idiopathic interstitial pneumonia.
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ABSTRACT: Idiopathic interstitial pneumonias (IIP) represent a complex group of relatively rare entities with similar clinical, vaguely similar radiographic and differing histologic features. The recent international multidisciplinary consensus statement produced by the American Thoracic Society/European Respiratory Society aiming to standardize the classification of IIP recognizes nonspecific interstitial pneumonia (NSIP) as a provisional category. While not representing a single disease, but rather a collection of pathologic processes with similar histomorphology, NSIP has been a great source of confusion for pulmonologists, radiologists, and pathologists. Lacking diagnostic clinical or radiographic features, NSIP is an IIP with recognizable and reproducible morphologic patterns different from usual interstitial pneumonia (UIP)-pattern as well as other disease patterns. And while overlap with UIP-pattern can be seen in individuals with multiple biopsy samples, those with either cellular or fibrosing variants of NSIP have a better prognosis than UIP-pattern patients. A morphologic diagnosis of NSIP-pattern alerts the clinician to a wide spectrum of potential clinical possibilities and enables researchers to study both this fibrosing interstitial pneumonia pattern and the more common and deadly UIP-pattern separately. Thus, this provisional category is useful to both clinicians and researchers.Current opinion in pulmonary medicine 10/2004; 10(5):441-6. · 3.08 Impact Factor -
Article: Primary paraganglioma of the lung.
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ABSTRACT: There are few reported cases of primary pulmonary paraganglioma in the pathology literature. Given the historical confusion surrounding bronchial tumors, widespread use of the term "chemodectoma" and classification of these lesions as paraganglioma in an outdated World Health Organization classification of lung tumors, the recognition of tumors arising from paraganglia within the lung has not been accepted by leading authorities. We present a well-documented case of a primary pulmonary paraganglioma with typical morphologic features and a supporting immunohistochemical profile. The 0.9 cm endobronchial tumor was submucosal and composed of nests of ovoid cells with abundant eosinophilic cytoplasm, cytoplasmic vacuoles, round to oval nuclei with speckled chromatin, and occasional conspicuous nucleoli. The nests of cells were surrounded by thin-walled vascular channels and stellate spindle cells. The ovoid cells showed strong diffuse staining for chromogranin A, synaptophysin, and faint staining for S-100; they were negative for cytokeratin AE1/AE3, Cam 5.2, and epithelial membrane antigen. The stellate spindle cells stained intensely positive for S-100 protein. A critical review of reported cases of pulmonary chemodectomas and paragangliomas in the English literature features few, if any, well-documented examples. While this exceedingly rare tumor should be discerned from carcinoid tumor, it remains unknown if primary pulmonary paragangliomas behave aggressively like intra-abdominal extra-adrenal paragangliomas, or in a more indolent manner observed with extra-adrenal paragangliomas in other locations.Annals of Diagnostic Pathology 09/2004; 8(4):237-41. · 0.88 Impact Factor -
Article: Pathologic characteristics of drug-induced lung disease.
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ABSTRACT: The surgical pathologist's role in the diagnosis of adverse pulmonary and pleural drug effect requires an appreciation of the clinico-radiologic scenario and particular knowledge of morphologic patterns of lung injury. Bronchoscopic biopsies may be helpful in some cases of DAD, eosinophilic pneumonia, or OP. Extrapolating patterns of lung involvement from small biopsies and cytologic preparations often is difficult and surgical lung biopsy is required. Although lung biopsies are not pathognomonic for drug toxicity and correlation with clinical, laboratory, and radiologic data is required, they can be a powerful tool in the evaluation of suspected drug-induced pulmonary disease by helping to exclude underlying disease or infection and documenting the pattern of lung injury. The latter information is helpful in making the diagnosis of drug toxicity as well as guiding the optimal management of the patient.Clinics in Chest Medicine 04/2004; 25(1):37-45. · 3.28 Impact Factor -
Article: Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers.
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ABSTRACT: 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.American Journal of Respiratory Cell and Molecular Biology 10/2003; 29(3 Pt 1):331-43. · 5.13 Impact Factor -
Article: Screen-detected adenocarcinoma of the lung. Practical points for surgical pathologists.
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ABSTRACT: Recent technological advances in thoracic radiology and surgery have altered the types of lung specimens handled by cytologists and surgical pathologists. Increasing numbers of individuals with small peripheral adenocarcinomas undergo minimally invasive diagnostic procedures and, in some instances, minimally invasive surgical procedures. The pathologist's role in early lung adenocarcinoma research is central, as clinical and investigational studies depend more than ever on subtle pathologic distinctions. Establishing a diagnosis of malignant neoplasm on samples from fine-needle aspiration, core biopsy, or frozen section is fraught with new considerations, and surgically resected adenocarcinomas must be typed according to the recently revised World Health Organization classification. Familiarity with small glandular proliferations, including the putative precursor lesion atypical adenomatous hyperplasia, will prevent misdiagnoses and untoward impact on tumor staging, therapy, and outcome studies.American Journal of Clinical Pathology 07/2003; 119 Suppl:S39-57. · 2.60 Impact Factor
Top co-authors
Top Journals
Institutions
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2010
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Harvard University
- Department of Medicine Brigham and Women's Hospital
Boston, MA, USA
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2006–2007
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Fox Chase Cancer Center
- Department of Pathology
Philadelphia, PA, USA
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2005–2006
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Memorial Sloan-Kettering Cancer Center
- Department of Pathology
New York City, NY, USA -
Cornell University
- Cardiothoracic Surgery
Ithaca, NY, USA
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2004
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New York Presbyterian Hospital
New York City, NY, USA
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2003–2004
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Weill Cornell Medical College
- Department of Pathology and Laboratory Medicine
New York City, NY, USA
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