Biomedical subjects

Eugene J Mark

Publications and source records attributed to Eugene J Mark.

40 records · Page 3Linked to original sources

PubMed2002

Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules.

The salient histopathologic features of low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include complex glandular structures and morules with biotin-rich optically clear nuclei. Interestingly, these characteristic features are shared by the cribriform-morular variant of papillary thyroid carcinoma, whose morphology is identical to that of familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore, the single reported case of lung cancer associated with FAP was L-FLAC/WDFA. These observations lead us to hypothesize that up-regulation of the Wnt signaling pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11 cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high-grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta-catenin. All cases of L-FLAC/WDFA showed predominantly aberrant nuclear/cytoplasmic expression, especially in budding glands and morules, whereas six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic expression restricted to the distal branching airway epithelium. Mutational analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA showed a point mutation at codon 34 and codon 37 in two cases, respectively. The present study indicates that up-regulating disturbances in the Wnt signaling pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L-FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that of the developing fetal lung airway. With the expression pattern of beta-catenin as a marker, most cases of H-FLAC as well as CAC appear to have different oncogenic pathways from cases of L-FLAC/WDFA. The present study together with other available data also suggests that abnormal up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors with morular formation from a variety of anatomic sites.

Adenocarcinoma↗

PubMed2002

Pulmonary neuroendocrine carcinomas. A review of 234 cases and a statistical analysis of 50 cases treated at one institution using a simple clinicopathologic classification.

CONTEXT: Primary pulmonary neuroendocrine tumors are traditionally classified into 3 major types: typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LC) or small cell neuroendocrine carcinoma (SC). Confusion arises frequently regarding the malignant nature of TC and the morphologic differentiation between AC and LC or SC. OBJECTIVE: To provide clinicopathologic evidence to streamline and clarify the histomorphologic criteria for this group of tumors, emphasizing the prognostic implications. PATIENTS: To minimize variability in diagnostic criteria and treatment plans, we analyzed a group of patients whose diagnosis and treatment occurred at a single institution. We reviewed 234 cases of primary pulmonary neuroendocrine tumors and thoroughly studied 50 cases of resected tumors from 1986 to 1995. RESULTS: On the basis of morphologic characteristics and biologic behaviors of the tumors, we agree with many previous investigators that these tumors are all malignant and potentially aggressive. Based on our accumulated data, we have modified Gould criteria and reclassified these tumors into 5 types: (1) well-differentiated neuroendocrine carcinoma (otherwise called TC) (14 cases, with less than 1 mitosis per 10 high-power fields [HPF] with or without minimal necrosis); (2) moderately differentiated neuroendocrine carcinoma (otherwise called low-grade AC) (6 cases, with less than 10 mitoses per 10 HPF and necrosis evident at high magnification); (3) poorly differentiated neuroendocrine carcinoma (otherwise called high-grade AC) (10 cases, with more than 10 mitoses per 10 HPF and necrosis evident at low-power magnification); (4) undifferentiated LC (5 cases, with more than 30 mitoses per 10 HPF and marked necrosis); and (5) undifferentiated SC (15 cases, with more than 30 mitoses per 10 HPF and marked necrosis). The 5-year survival rates were 93%, 83%, 70%, 60%, and 40% for well, moderately, and poorly differentiated, and undifferentiated large cell and small cell neuroendocrine carcinomas, respectively. We found nodal metastasis in 28% of TC in this retrospective review, a figure higher than previously recorded. CONCLUSION: Using a grading system and terms comparable to those used for many years and used for neuroendocrine tumors elsewhere in the body, we found that classification of pulmonary neuroendocrine carcinomas as well, moderately, poorly differentiated, or undifferentiated provides prognostic information and avoids misleading terms and concepts. This facilitates communication between pathologists and clinicians and thereby improves diagnosis and management of the patient.

Adult↗

PubMed2002

Cystic adenomatoid change is common to various forms of cystic lung diseases of children: a clinicopathologic analysis of 10 cases with emphasis on tracing the bronchial tree.

CONTEXT: Congenital cystic adenomatoid malformation, intralobar sequestration, extralobar sequestration, bronchopulmonary foregut malformation, bronchial atresia, and lobar emphysema generally are treated as separate entities, but there are commonalities among them. OBJECTIVE: To clarify the identity of congenital cystic adenomatoid malformation in relation to other cystic diseases. DESIGN: We studied 10 consecutive cases of surgically resected cystic lung disease in children. We studied the bronchial and vascular trees by mapping bronchi, pulmonary blood vessels, systemic blood vessels, the size and configuration of cysts, and associated scarring. RESULTS: The cystic lesions proved to be the following: 1 case of congenital cystic adenomatoid malformation, 2 cases of bronchial atresia with congenital cystic adenomatoid malformation, 1 hybrid case of congenital cystic adenomatoid malformation and intralobar sequestration, 1 case of intralobar sequestration with an aberrant hilum, 3 cases of intralobar sequestration with bronchial obliteration, 1 case of lung abscess, and 1 case of lobar emphysema. Congenital cystic adenomatoid malformation was the sole pathologic diagnosis in 1 case, but 7 other specimens had cystic adenomatoid change to various degrees. There was no bronchial connection between the cystic lesions and the patient's airway in 8 cases. The bronchial tree was absent in the cystic lung in 2 cases. Bronchus tapered into scar near the cystic lesion in 4 cases. Only 1 case had no significant bronchial abnormality. CONCLUSION: The high incidence of cystic adenomatoid change in cystic lung disease associated with an abnormality of the bronchial tree suggests that cystic adenomatoid change may develop together with and be related to other congenital or acquired conditions in the lung.

Bronchogenic Cyst↗

PubMedDate not supplied

CT-histologic correlation of the ATS/ERS 2002 classification of idiopathic interstitial pneumonias.

The American Thoracic Society and the European Respiratory Society 2002 classification defines the histologic patterns that provide the basis for a clinico-radiologic-pathologic diagnosis of an idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis is the clinical term for usual interstitial pneumonia, the characteristic histologic pattern is interstitial fibrosis with temporal heterogeneity, and the radiologic pattern is basal and subpleural areas of ground-glass and reticular attenuation and honeycomb pattern. Nonspecific interstitial pneumonia has cellular or fibrosing patterns of chronic inflammation with temporal homogeneity; the radiologic pattern is subpleural and basal areas of ground-glass and reticular attenuation. Lymphoid interstitial pneumonia results from lymphocyte interstitial infiltration; CT demonstrates ground-glass attenuation and nodular interlobular septal thickening. Respiratory bronchiolitis-associated interstitial lung disease is characterized by bronchiolocentric alveolar macrophage accumulation; CT shows centrilobular ground-glass attenuation. Desquamative interstitial pneumonia is characterized by alveolar macrophage accumulation with predominantly lower zone ground-glass attenuation seen on CT scans. Cryptogenic organizing pneumonia is characterized radiologically by peribronchial ground-glass attenuation and subpleural consolidation. Acute interstitial pneumonia is the clinical term for idiopathic diffuse alveolar damage; the exudative phase is characterized radiologically by diffuse ground-glass attenuation and dependent consolidation, with the additional feature of lung architectural distortion in the organizing phase. Ideally, diagnosis of an idiopathic interstitial pneumonia should be rendered only after all clinico-radiologic-pathologic data have been reviewed.

Adult↗