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Eugene J Mark

Publications and source records attributed to Eugene J Mark.

At least 19 recordsLinked to original sources
PubMed2006

Resident physician opinions on autopsy importance and procurement.

The national decline in hospital autopsy cases negatively impacts physician education and medical quality control to an unknown degree. The current non-medicolegal autopsy rate is less than 5% of hospital deaths. This study compares internal medicine and pathology resident physician perceptions of the autopsy, including the importance, procurement, technique, and the pathologist-internist interaction. An 84-item survey based on autopsy literature was designed, piloted, and distributed to 214 residents at a single 800+ bed tertiary care academic teaching hospital (Massachusetts General Hospital, Boston) to accomplish this goal. Completed surveys were obtained from 72% of medicine (n = 118) and 84% of pathology (n = 42) residents. Residents strongly agree on the importance of autopsies for education, answering clinical questions, public health, and research. Autopsy rates are deemed inadequate. Internists are comfortable requesting autopsies, but report insufficient guidance and difficulty with answering technical questions. Although not requested on all hospital deaths, internists are more likely to initiate an autopsy request than a decedent's family, and worry significantly less about institutional costs and malpractice litigation than pathologists believe. Internists expressed interest in having an instructional brochure to give families, observing an autopsy, and having increased communication and support with autopsies from pathology residents. The main reasons why autopsy consent is not requested (it is unpleasant, cause of death is known, family is upset or seems unwilling) and why families refuse (patient has suffered enough, body may be handled disrespectfully, religious/moral objections, lack information) were similar for both resident groups. Despite their decline, autopsies still remain important to medicine as indicated by internal medicine and pathology residents at a large academic center. Improving autopsy education, enhancing availability of resources, and strengthening the pathologist-internist collaboration may serve to heighten awareness and ultimately procurement.

Attitude of Health Personnel↗
PubMed2006

Mustard lung secrets: long term clinicopathological study following mustard gas exposure.

Considering the undefinite nature of lung pathology in patients exposed to sulfur mustard (SM) many years after exposure, we conducted this study to document and quantify lung disease in this setting. In a cross sectional study, we selected 23 patients exposed to SM gas approximately 14 years ago during the Iran-Iraq war (1980-1988). We studied their clinical history, physical examination, pulmonary function test (PFT), high-resolution computed tomography scan (HRCT) of the chest, bronchoscopy, and bronchoalveolar lavage (BAL) sampling, and transbronchial lung biopsies. Other potential causes of lung disease, including smoking of cigarettes, were excluded. All 23 patients were symptomatic with cough, dyspnea, and/or felt tight in the chest. All of them had significant air trapping in HRCT and a marked increase of residual volume in PFT. The most common inflammatory cell in BAL fluid was neutrophil (88%). Of the 23 cases, there was sufficient tissue for detailed evaluation in 22. Histologically, 11 cases showed airway epithelial injury, and nine of the 14 lung biopsies with alveoli had histopathological changes diagnosable as organizing pneumonia (OP) or bronchiolitis obliterans OP (BOOP). Two out of 14 cases showed changes suggestive of OP. Inhalation of SM can lead to persistant and clinically significant lung disease, including bronchial mucosal injury and OP, many years after exposure.

Adult↗
PubMed2006

Epidermal growth factor receptor mutation testing in the care of lung cancer patients.

As the literature about epidermal growth factor receptor (EGFR) mutations grows and screening for mutations becomes increasingly integrated into clinical care, it is important to examine how best to do somatic mutational analyses and how best to use the test results in clinical decision making. We began offering mutation screening by comprehensive direct sequence analysis of exons 18 to 24 of the tyrosine kinase domain of EGFR in August 2004 as part of clinical cancer care and protocol therapy at our institutions. All identified potential mutations are confirmed with three to five independent PCRs of the original genomic DNA sample and, if not previously noted in the literature, are compared with the patient's germ-line DNA to ensure the finding is somatic. We formally analyzed the first 100 patients to undergo EGFR sequence analysis and found that testing was feasible and significantly affected the treatment of patients with non-small cell lung cancer (NSCLC). Patients harboring EGFR mutations were significantly more likely to receive recommendations for therapy with EGFR tyrosine kinase inhibitors (i.e., gefitinib or erlotinib) than patients without mutations. However, negative EGFR test results did not prevent physicians from administering these agents to selected patients. Ideally, a standardized technique for mutation testing could be developed, with demonstrated reproducibility and validity. Clinical trials incorporating molecular diagnostics are ongoing to assess the efficacy of EGFR tyrosine kinase inhibitors as first-line therapy for metastatic NSCLC and as adjuvant therapy for early-stage resected NSCLC. It is likely that mutation testing and other molecular analyses will be most useful in these two clinical situations.

Carcinoma, Non-Small-Cell Lung↗
PubMed2006

Pathological recognition of diffuse malignant mesothelioma of the pleura: the significance of the historical perspective as regards this signal tumor.

Diffuse malignant mesothelioma (DMM) is a distinctive tumor which provides an uncommon opportunity to observe the gradual appreciation and increasing incidence of a new disease. DMM is a new disease. One cannot comment intelligently about the pathology of sporadic cases that might have occurred before the beginnings of anatomic pathology, but we do know that there were so few cases before 1930 that the very existence of the disease was not accepted in general before 1930 and not accepted by all pathologists even up until 1960. Because DMM is increasing on a worldwide basis and is making its appearance in the developing world, where it has not previously been diagnosed, appreciation of how the disease came to be noticed sheds light on its causation. As a signal tumor for exposure to asbestos, and knowing that all special exposures contribute to the development of the disease, knowledge of its continuing escalation underscores the importance of recognition of previously unimplicated or occult exposures for reasons of public health in both developed and developing countries.

Asbestos↗
PubMed2006

Distinguishing benign mesothelial hyperplasia from neoplasia: a practical approach.

This paper examines the spectrum of challenges that confront the diagnostic surgical pathologist in distinguishing benign mesothelial hyperplasia from malignant mesothelioma. The current state of the art with respect to the morphological, immunohistological, and molecular features that can assist in the evaluation of benign and malignant pleural disease is examined. Practical guidelines are offered that should reduce the risk of diagnostic error in this problematic area of surgical pathology.

Diagnosis, Differential↗
PubMed2006

Tracheobronchial gland tumors.

BACKGROUND: Tracheal tumors are uncommon, making up only 0.2% of all respiratory malignancies in the United States. One consequence of this low incidence is that few centers accumulate meaningful experience. Another is the lack of awareness of effective therapy. Bronchial gland tumors demonstrate oncologic diversity and include benign, low-grade, and high-grade malignant tumors. METHODS: We reviewed the present knowledge of bronchial gland tumors of the trachea, carina, and bronchi, including the epidemiology, presentation, evaluation, tumor types, and treatment options. RESULTS: The malignant bronchial gland tumors, adenoid cystic carcinoma and mucoepidermoid carcinoma, are far more common than benign mucinous cystadenoma or pleomorphic adenoma. Complete resection of localized tumors has excellent long-term results in symptomatic benign tumors. The disease-free survival after resection of malignant tumors is limited by distant metastasis and regional disease, while local recurrence is uncommon. Postoperative mediastinal radiation is now accepted adjuvant therapy. Experience at our institute demonstrates a significant survival advantage for patients with complete resection compared to unresectable patients. CONCLUSIONS: Expanding knowledge of diagnostic evaluation and surgical therapy can improve the long-term survival of patients with tracheobronchial gland tumors.

Bronchial Neoplasms↗
PubMed2005

Endothelial nitric oxide synthase expression in pulmonary capillary hemangiomatosis.

Pulmonary capillary hemangiomatosis (PCH) is an unusual disorder characterized by the proliferation of capillaries in the alveolar septa and pulmonary interstitium. Originally conceived as a primary idiopathic disorder of the pulmonary microcirculation, recent studies have demonstrated that PCH may be associated with other pathologies. Nitric oxide (NO) is a gaseous free radical with protean biological effects that is released during the intracellular conversion of arginine to citrulline. Nitric oxide synthases (NOS) mediate the production of NO and the release of NO in the microvasculature is specifically catalyzed by endothelial NOS (NOS-III). As NOS contributes to angiogenesis and is reduced in the hypertensive pulmonary microcirculation, we examined the expression of NOS-III protein in situ in the lungs of patients with PCH. Reduced microvascular expression of NOS-III protein by endothelial cells was observed in 4/6 (67%) cases of PCH, and all of these showed concomitant pulmonary vascular hypertensive remodeling. In 2/6 (33%) cases of PCH with no morphologic evidence of pulmonary hypertensive arteriopathy, endothelial expression of NOS-III protein was judged to be either minimally reduced or normal. These findings suggest that NOS-III is specifically reduced in PCH when pulmonary arterial hypertensive remodeling is concomitantly present.

Aged↗
PubMed2005

Primary pulmonary lymphoma.

BACKGROUND: Primary pulmonary lymphoma is a rare disease. The clinical characteristics, methods of treatment, and outcomes are not well elucidated. METHODS: A retrospective review of primary pulmonary lymphoma cases at a single institution from 1990 to 2002 was performed. RESULTS: Eighteen patients were included, with a mean follow-up of 2.9 years. Fourteen patients had mucosa-associated lymphoid tissue (MALT) lymphoma, 2 had large cell transformation of sheet cells in MALT lymphoma, and 1 each had Hodgkin's disease and follicular lymphoma. Computed tomography-guided biopsy was diagnostic in only two of eight attempts. Eleven patients had disease confined to the pulmonary parenchyma, and 7 had parenchymal disease as well as mediastinal lymphadenopathy. Treatment methods included observation only (n = 1), surgery only (n = 6), surgery plus chemotherapy (n = 8), surgery plus radiotherapy (n = 1), and surgery plus chemotherapy plus radiotherapy (n = 2). Kaplan-Meier estimate of median time to disease recurrence or death was 6 years. Only 1 patient died of disease-related causes. Patients who had bilateral disease were more likely to have recurrent disease or death (p = 0.03). CONCLUSIONS: A wide range of treatments were used for patients with generally MALT lymphoma, resulting in good outcomes, and recurrent disease was well controlled.

Adult↗
PubMed2005

Lung transplantation biopsy specimens with bronchiolitis obliterans or bronchiolitis obliterans organizing pneumonia due to aspiration.

CONTEXT: Bronchiolitis obliterans (BO) is generally thought to be a marker of chronic airway rejection in patients who have undergone lung transplantation. Bronchoscopic biopsy specimens, by virtue of their small size, may sample only BO and not a lesion of bronchiolitis obliterans organizing pneumonia (BOOP). A role for ongoing chronic infection or aspiration has also been suggested, and the distinction of these etiologies may be difficult clinically and pathologically. OBJECTIVE: To investigate the etiology of BO and BOOP in lung transplantation patients who had chronic aspiration. DESIGN: This is a clinicopathologic study of 7 patients who had undergone lung transplantation in which biopsy findings suggested the possibility of chronic airway rejection but in which aspiration was subsequently proven as a cause of the bronchiolar disease. RESULTS: All patients were men, who ranged in age from 19 to 57 years. A clinical diagnosis of aspiration was considered based on history, acid reflux testing, and radiographic findings in all 7 patients. Three patients had BO and 4 patients had BOOP. Histiocytic giant cells or foreign material was absent. The interval from transplantation to BO ascribed to aspiration ranged from 2.5 months to 7 years. The patients were treated aggressively with medication for gastroesophageal reflux disease. Their respiratory function and chest radiography results improved. CONCLUSION: Although BO may be a manifestation of rejection, it may also be a manifestation of aspiration. Because the latter is potentially correctable, aspiration should be considered etiologically in lung transplantation patients with either BO or BOOP. Reliable distinction between aspiration-related or rejection-related BO and BOOP cannot be made on morphologic grounds alone. Clinical and radiologic correlations are indicated to establish the distinction.

Adult↗
PubMed2004

Biotin-rich, optically clear nuclei express estrogen receptor-beta: tumors with morules may develop under the influence of estrogen and aberrant beta-catenin expression.

Recent studies have indicated that aberrant beta-catenin expression may be a common denominator for the morular formation of tumors from various anatomic sites. The evidence for the influence of female sex hormones in the formation of morules has been circumstantial, most previous studies having failed to demonstrate female sex hormone receptors in the morular cells. We investigated a possible role of estrogen receptor (ER)-beta in the occurrence of tumors that form morules with biotin-rich optically clear nuclei (BROCN)(BROCN-family tumors) and its possible relationship with aberrant nuclear/cytoplasmic (N/C) beta-catenin expression. We immunostained 14 BROCN-family tumors, including 6 low-grade adenocarcinomas of the fetal lung type, 3 papillary thyroid carcinomas of cribriform-morular variant (CMV), 2 ovarian endometrioid tumors, 2 colonic adenocarcinomas, and 1 gallbladder adenoma, as well as 4 cases of endometrial tissue with BROCN during gestation, for ERbeta, ERalpha, progesterone receptor (PgR), beta-catenin, and, on a subset of cases, c-Fos and MIB-1 as well. BROCN in all 18 cases expressed ERbeta but not ERalpha or PgR. In the BROCN-family tumors, the morular cells and budding glandular cells expressed ERbeta in the cytoplasm and BROCN, which overlapped with the N/C expression pattern of beta-catenin. Beta-catenin showed only membranous expression in the endometrial glands during gestation. In CMV and ovarian endometrioid tumors, nuclear expression of ERalpha and PgR were observed in association with N/C beta-catenin expression only in the glandular component. C-Fos was also constantly and strongly expressed in BROCN in all cases examined. The MIB-1 labeling index was low in the morular area, ranging from 1% to 3%. The present study indicates that N/C co-localization of ERbeta and beta-catenin is a feature common to the morules with BROCN that appear in the BROCN-family tumors from various anatomic sites. Whether the estrogen-signaling pathway and the Wnt-signaling pathway have crosstalk, cooperating in the development of the BROCN-family tumors, awaits further study.

Adult↗
PubMed2004

Aberrant nuclear/cytoplasmic localization and gene mutation of beta-catenin in classic pulmonary blastoma: beta-catenin immunostaining is useful for distinguishing between classic pulmonary blastoma and a blastomatoid variant of carcinosarcoma.

It is now known that gene mutation of beta-catenin with subsequent nuclear/cytoplasmic (N/C) overaccumulation of the protein plays an important role in tumorigenesis of various organs. We recently demonstrated that low-grade adenocarcinoma of the fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA), the epithelial prototype of classic pulmonary blastoma (CPB), shows N/C localization of beta-catenin with genetic mutation. This prompted us to further investigate the state of beta-catenin abnormality in CPB and related neoplasms. We studied 9 lung tumors previously diagnosed as biphasic pulmonary blastoma (PB). Histologically, 4 cases (median age 34 years) were CPB with l-FLAC/WDFA as the epithelial component, whereas 5 cases (median age 65 years) were a variant of carcinosarcoma with high-grade FLAC/clear cell adenocarcinoma with fetal lung features as the epithelial component, which we term the blastomatoid variant of carcinosarcoma (BCS). Immunohistochemically, all 4 CPBs showed aberrant N/C localization of beta-catenin both in the epithelial and mesenchymal components, with especially high staining intensity in the budding glands and morules. In contrast, all 5 BCSs showed preserved or diminished membranous expression and no significant N/C expression of beta-catenin in the epithelial component, and absent or focal N/C expression of beta-catenin in the mesenchymal component. Mutational analysis of exon 3 of the beta-catenin gene revealed that 3 CPBs harbored missense mutations (S29F, S37F, and S37F), whereas none of the 5 BCSs had this mutation. This study suggests that beta-catenin gene mutations may play a role in the tumorigenesis of CPB. Although CPB and BCS have often been grouped together as biphasic PB, they are different entities based on immunohistochemical and molecular analysis of beta-catenin. Immunostaining for beta-catenin is useful for the discrimination.

Adult↗
PubMed2004

The role of open-lung biopsy in ARDS.

STUDY OBJECTIVES: The role of open-lung biopsy in ARDS has been questioned due to potentially high morbidity and low diagnostic yield. The goals of this study were to better define the frequency of unexpected diagnoses made by open-lung biopsy, the frequency biopsy results lead to a change in clinical management, and the frequency of procedural complications. DESIGN: Case series. SETTING: A large tertiary referral center. PATIENTS: All individuals with available records undergoing open-lung biopsy between 1989 and 2000 for evaluation of ARDS based on the American-European Consensus Conference definition. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The mean age in this cohort of 57 patients was 53 years (SD, 18 years) with PaO(2)/fraction of inspired oxygen ratio of 145 mm Hg (SD, 61 mm Hg) at the time of biopsy. A pathologic diagnosis other than diffuse alveolar damage or fibroproliferation was found in 60% of patients. The most common alternative diagnoses were infection (n = 8), alveolar hemorrhage (n = 5), and bronchiolitis obliterans organizing pneumonia (n = 5). Alternative diagnoses were as frequent in immunocompetent as immunosuppressed hosts (60% vs 59%, respectively). Biopsy results led to a change in management in the majority of patients, with addition of specific therapy in 60% and withdrawal of unneeded therapy in 37%. Although the overall complication rate was 39%, major complications occurred in only 7% of cases. No deaths were attributable to the procedure. CONCLUSIONS: In selected patients with clinical ARDS, open-lung biopsy can be performed safely, often reveals an unsuspected diagnosis, and frequently leads to alterations in therapy.

Biopsy↗