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D B Flieder

Publications and source records attributed to D B Flieder.

16 recordsLinked to original sources
PubMed2006

EU-USA pathology panel for uniform diagnosis in randomised controlled trials for HRCT screening in lung cancer.

Randomised controlled trials for lung cancer screening using high-resolution computed tomography are now underway. In order to allow effective future comparison of the different trials, as well as strengthening conclusions based upon the analysis of larger data sets, uniformity and consistency of pathology diagnosis are essential. The aim of the present study was to determine the effectiveness of the learning process in this difficult area of diagnostic pathology. Eight pathologists received two CD-ROMs, each with digital images of 30 cases. After diagnosing the first series, selected background reading was provided. Kappa (kappa) scores were calculated for each pathologist and category, and were compared to the consensus score. The readings of the first series showed a moderate agreement kappa score: mean+/-sd for category numbers 8 (all eight categories) and 2 were 0.53+/-0.05 and 0.65+/-0.04, respectively. The kappa 2 score distinguished between categories denoting benign and malignant lesions. The second series resulted in a good agreement kappa score: 0.65+/-0.06 for category number 8 and 0.81+/-0.02 for category number 2. In conclusion, this study demonstrates that screen-detected cases pose particular problems for pathologists and that a trained pathology panel serving randomised controlled trials is likely to lead to more consistent and accurate tissue diagnosis.

Adenocarcinoma↗
PubMed2003

Celecoxib, a selective cyclo-oxygenase-2 inhibitor, enhances the response to preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer.

PURPOSE: Preclinical studies suggest that treatment with a selective cyclo-oxygenase-2 (COX-2) inhibitor may augment the antitumor effects of chemotherapy. In this study, patients with non-small-cell lung cancer (NSCLC) were preoperatively treated with celecoxib in combination with chemotherapy. End points were toxicity, response rates, and measurement of intratumoral levels of prostaglandin E2 (PGE2). METHODS: In this phase II trial, 29 patients with stages IB to IIIA NSCLC were treated with two preoperative cycles of paclitaxel and carboplatin, as well as daily celecoxib, followed by surgical resection. Levels of PGE2 in the primary tumors and adjacent normal lung tissue were compared in 17 study patients versus 13 controls, who received preoperative paclitaxel/carboplatin without celecoxib. RESULTS: All patients completed preoperative chemotherapy, and 26 completed preoperative celecoxib. The overall clinical response rate was 65% (48% with partial response; 17% with complete response). Grade 3 or 4 neutropenia was observed in 18 patients (62%). Twenty-eight patients were explored and underwent complete resection of their tumors. There were no complete pathologic responses, but seven patients (24%) had minimal residual microscopic disease. The addition of celecoxib to a regimen of paclitaxel and carboplatin abrogated the marked increase in levels of PGE2 detected in primary tumors after treatment with paclitaxel and carboplatin alone. CONCLUSION: In comparison with historically reported response rates, these data suggest that the addition of a selective COX-2 inhibitor may enhance the response to preoperative paclitaxel and carboplatin in patients with NSCLC. Moreover, treatment with celecoxib 400 mg twice daily was sufficient to normalize the increase in PGE2 levels found in NSCLC patients after treatment with paclitaxel and carboplatin. Confirmatory trials are planned.

Adult↗
PubMed2000

Lung tumors with neuroendocrine morphology. A perspective for the new millennium.

Pulmonary neuroendocrine cell proliferations represent a spectrum of lesions ranging from reactive processes to highly malignant carcinomas. The histogenesis and classification of these lesions is controversial and confusing. Radiologists are performing many diagnostic fine needle aspirations and biopsies, and must be familiar with these tumors. This article describes the various lesions and provides guidelines for their differential diagnosis.

Humans↗
PubMed2000

Small peripheral glandular lesions detected by screening CT for lung cancer. A diagnostic dilemma for the pathologist.

The early detection of lung cancer by helical CT provides an important opportunity for radiologic-pathologic and clinical correlation of borderline glandular lesions. Little is known about the clinical course of atypical adenomatous hyperplasia, solitary noninvasive, nonmucinous BAC, and early-phase invasive adenocarcinomas, therefore, a single protocol for specimen handling and a central tissue registry are essential. The most important separation among the various types of adenocarcinoma is the diagnosis of BAC, a potentially curable malignancy, from invasive adenocarcinoma. Therefore, for small lesions of 2 cm or less, the entire tumor should be processed. For larger lesions, one section per centimeter should be sampled, and if the initial sections show a purely lepidic growth pattern, additional sections should be taken to exclude an invasive component. If foci of invasion are identified, the tumor should be classified as an adenocarcinoma with bronchioloalveolar features. At the International Conference on Screening for Lung Cancer held in October 1997, it was recommended that an international panel be used to reach consensus on difficult lesions of the lung detected by CT screening, and that a tissue bank of these lesions be established to ensure further clinical, radiographic, light microscopic, immunohistochemical, and molecular studies of putative precursor lesions and small carcinomas. Through the collection of these lesions, we can further our understanding of the biologic behavior of lung cancer, particularly because little is known about the progression from a purely lepidic growth pattern to invasive adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population. METHODS: Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS (and other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke. RESULTS: When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P =. 02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year = ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure. CONCLUSIONS: A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).

Adult↗
PubMed1999

Pulmonary dirofilariasis: a clinicopathologic study of 41 lesions in 39 patients.

Forty-one cases of pulmonary dirofilariasis in 39 patients are presented. The patients, all Americans, were between 8 and 80 years old (median, 58 years), including 23 men and 16 women. Twenty-two patients were asymptomatic (56%), and the pulmonary nodule was discovered on chest radiographs during a routine physical examination. Seventeen patients (44%) presented with respiratory symptoms or systemic complaints. Peripheral eosinophilia was noted in only 10% of the patients. Radiographically, most lesions were located in the right lung (76%), with a predilection for the lower lobe. In five patients multifocal nodules were seen. All patients underwent thoracotomy with excisional lung biopsy or lobectomy. Pathologically, all cases featured a histiocyte-rimmed necrotic nodule containing fragments of a partially degenerated Dirofilaria immitis. In addition, adjacent lung parenchyma showed morphological features suggestive of other pulmonary processes such as extrinsic allergic alveolitis and/or pulmonary vasculitis syndromes. Three of the five patients with multiple nodules had solitary dirofilarial nodules and adjacent non-small cell carcinomas. The cases presented herein highlight the variable morphological features seen in human pulmonary dirofilariasis and emphasize the need to consider this diagnosis in all cases of necrotizing granulomas of the lung.

Adolescent↗
PubMed1999

Idiopathic fibroinflammatory (fibrosing/sclerosing) lesions of the mediastinum: a study of 30 cases with emphasis on morphologic heterogeneity.

The clinicopathologic and immunohistochemical findings in 30 cases of idiopathic fibroinflammatory lesions of the mediastinum are presented. There were 17 male and 13 female patients between 10 and 64 years of age; 19 were African-American, and 10 were Caucasian. Clinically, respiratory and/or systemic symptoms including cough, shortness of breath, and fever were present in 28 patients. Five patients also presented with evidence of superior vena cava syndrome. All of the lesions involved the anterior mediastinum with radiographic evidence of hilar and paratracheal involvement in nine and five patients, respectively. Histologically, the lesions were characterized by an inflammatory fibrosing process that showed three distinctive histologic patterns. On the basis of the histologic pattern, they were subdivided into three distinct groups (stages). Stage I demonstrated edematous fibromyxoid tissue with numerous spindle cells, eosinophils, mast cells, lymphocytes, plasma cells, and thin-walled blood vessels; Stage II showed thick glassy bands of haphazardly arranged collagen with focal interstitial spindle cells, lymphocytes, and plasma cells; and Stage III was characterized by dense acellular collagen with scattered lymphoid follicles and occasional dystrophic calcification. Immunohistochemical studies in 17 cases highlighted large numbers of vimentin- and actin-positive spindle cells and capillary-like vessels in Stage I lesions, with fewer numbers of vimentin-positive, actin-negative spindle cells and vessels in Stage II lesions. Our findings suggest that "sclerosing mediastinitis" represents the final stage of an evolving, dynamic process with different morphologic appearances akin to abnormal wound healing. Thus, we propose the term fibroinflammatory lesion of the mediastinum to convey the true nature of the process.

Adolescent↗
PubMed1998

Pleuro-pulmonary endometriosis and pulmonary ectopic deciduosis: a clinicopathologic and immunohistochemical study of 10 cases with emphasis on diagnostic pitfalls.

The clinical and pathological features of nine cases of pleuro-pulmonary endometriosis and the first case of pulmonary ectopic deciduosis are presented. The patients were all women between the ages of 27 and 74 years (median, 36 years) who presented with symptoms of catamenial pleural pain, shortness of breath, hemoptysis, or radiographically detected lung masses. Clinically, six patients were multiparous, one patient had pelvic endometriosis, and four patients had undergone prior pelvic surgical procedures, including dilatation and curettage. Radiographically, eight patients had pulmonary infiltrates or nodules, and four patients had pneumothorax. Three cases involved the visceral pleura and one case the parietal pleura. The other six cases, including the single case of ectopic deciduosis, involved the lung parenchyma. Histologically, the single or multifocal lesions were well circumscribed or infiltrative, nodular, cystic, or nodulo-cystic, and showed the characteristic features of proliferative or secretory endometrium with numerous mullerian metaplastic changes. Mucin stains were negative in five cases of endometriosis and in the single case of ectopic deciduosis. Immunohistochemical studies were performed in these same six cases using antibodies to epithelial, mesenchymal, vascular, and neuroendocrine markers. The glandular epithelium was decorated with antibodies to pan-cytokeratin, CK7, BER-EP4, ER, and PR, whereas the stromal cells showed positive staining for vimentin, actin, smooth muscle actin, desmin, ER, and PR. Follow-up information obtained in seven patients showed all women without recurrences after 1 to 20 years. The current study highlights the importance of recognizing intrathoracic endometriosis and ectopic deciduosis and properly assessing small biopsy specimens to avoid a misdiagnosis of malignancy.

Adult↗
PubMed1998

Primary cutaneous synovial sarcoma: a case report.

We present a case of synovial sarcoma involving the cutaneous tissue of the knee in an 18-year-old woman. The 2.5 cm tumor was locally excised and recurred six times over the following 24 years. The neoplasm involved the deep dermis with extension into the papillary dermis and superficial subcutis. The tumor was predominantly composed of spindle cells arranged in compact interdigitating fascicles and scattered epithelial nests were seen. Focal myxoid and hemangiopericytoma-like areas as well as numerous mast cells were identified. Spindle cells stained for vimentin, CAM 5.2, and epithelial membrane antigen, whereas epithelial nests only stained for CAM 5.2 and epithelial membrane antigen. Neither component was reactive for antibodies directed against desmin, muscle specific actin, smooth muscle actin, S-100 protein, CD-31, or CD-34. This newly reported location for this morphologically heterogeneous tumor creates potential diagnostic confusion with other primary neoplasms in these areas.

Adolescent↗
PubMed1998

Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid.

Neuroendocrine tumors of the lung embrace a spectrum from low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade categories of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). We studied 200 neuroendocrine lung tumors to critically evaluate the Arrigoni histologic criteria for AC using statistical analysis to delimit more rigorously an intermediate survival for AC between TC and the high-grade tumors of LCNEC and SCLC. Histologic features that might predict prognosis were used for Kaplan-Meier and Cox proportional hazards survival analysis, and an optimal mitotic range for AC was calculated. The optimal mitotic range for AC was 2 to 10 mitoses per 2 mm2 of viable tumor (10 high-power fields). Based on this finding, we collapsed mitoses into three categories (< 2; 2-10; > or = 11) and performed Cox multivariate analysis for all 200 neuroendocrine tumors. Mitotic counts were the only independent predictor of prognosis. Based on this analysis, we propose that AC be defined as a tumor with neuroendocrine morphology, mitotic counts between 2-10 per 2 mm2 of viable tumor (10 high-power fields), or coagulative necrosis. Using these criteria, the 200 neuroendocrine tumors were classified as 51 TC, 62 AC, 37 LCNEC, and 50 SCLC. The 5- and 10-year survival was 87% and 87% for TC, 56% and 35% for AC, 27% and 9% for LCNEC, and 9% and 5% for SCLC, respectively. After stratification for stage, survival for AC was significantly worse than for TC (p < 0.001); for LCNEC and SCLC it was significantly worse than for AC; but the survival for LCNEC was no different than that for SCLC.

Carcinoid Tumor↗
PubMed1998

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.

Aged↗
PubMed1998

Respiratory syncytial virus-associated infections in adult recipients of solid organ transplants.

BACKGROUND: Although respiratory syncytial virus (RSV) infection is known to cause severe pulmonary infections in bone marrow transplant recipients, less is known concerning its clinical course, diagnosis, and treatment in solid organ transplant recipients. METHODS: We have conducted a retrospective review of seven cases of RSV infection in adult recipients of solid organ transplants. Four patients received lungs, two received kidneys, and one received a heart. RESULTS: The most common presenting complaints were dyspnea (100%), cough (86%), and purulent sputum (57%). Physical findings included fever (43%), rales (100%), and wheezing (29%). Admission studies were significant for leukocytosis (29%), a left shift in the white blood cell differential (86%), and hypoxemia (mean PaO2 = 64). Chest radiographs were unchanged in 29% and showed infiltrates that were bilateral in 43% and unilateral in 29%. Pulmonary function tests in lung transplant recipients showed a mean fall in forced expiratory volume in 1 second of 26% and a fall in diffusion capacity for carbon monoxide of 24%. Five patients were treated with aerosolized ribavirin. Adverse events associated with treatment included wheezing (80%) and mild dyspnea (20%). The conditions of three of five treated patients were believed by their physicians to have improved 7 days after the initiation of therapy. One of the five treated patients died, and both untreated patients survived. CONCLUSIONS: RSV infection in this population has an extremely variable severity and clinical course, usually dominated by lower respiratory symptoms and obstructive airway disease. Ribavirin therapy is well tolerated, but its efficacy remains unknown.

Adult↗
PubMed1997

Treated Wegener's granulomatosis: distinctive pathological findings in the lungs of 20 patients and what they tell us about the natural history of the disease.

Patients with an established diagnosis of Wegener's granulomatosis (WG) sometimes undergo lung biopsy when the disease does not behave in the expected manner. Treatment affects the tissue reaction. The microscopic recognition of partially treated disease is important, as the absence of expected lesions may lead to nonspecific diagnoses and inappropriate management. The appearance of treated disease over time may offer insight into its histogenesis and natural history. We correlated clinical features and pulmonary histology in 20 patients with WG after they had been treated with corticosteroids or cyclophosphamide or both. All patients had inflammatory or fibrotic pulmonary disease resulting from WG, but only 4 (20%) had macronodular necrosis typical of WG. Serum antineutrophil cytoplasmic antibody (ANCA) was elevated in all patients in whom it was measured. We divided the pathological findings into (1) vasculitis, (2) extravascular necrosis, (3) bronchiolitis, and (4) other lesions, and further divided them into (a) diagnostic for active disease, (b) suspicious for active disease, (c) suspicious for healing disease, (d) suspicious for residual disease, and (e) possible disease. Diagnostic or suspicious vascular lesions occurred in 15 patients (75%) and included granulomatous vasculitis, capillaritis or suspicious capillaritis, and neutrophilic vasculitis. Diagnostic or suspicious extravascular lesions occurred in 12 patients (60%) and included palisading granuloma, microabscess, macronodular pathergic necrosis, giant cell nodules, and micronodular scars. The giant cell nodules and nodular scars were an unusual healing pattern of palisading granulomas. Diagnostic bronchiolar lesions occurred in 1 patient (6%) and suspicious lesions in 13 patients (65%), including three novel patterns of bronchiolitis fibrosa (BF): (1) BF with giant cells, (2) BF with hemosiderin, and (3) BF with micronodular scars. Other features related to WG included diffuse alveolar damage, peculiar alveolar fibrin, interstitial fibrosis, pneumonitis resembling usual interstitial pneumonitis, and lipoid pneumonia. Classic necrotic nodules and vasculitis of WG should not be anticipated after therapy, but the diagnosis of pulmonary WG after treatment may be made if the effects of treatment on histology are considered. Changes in anticipated histology are found after therapy as short as 6 days. The histology typically has muted features. BF develops in most patients and may reflect a salutary effect of therapy. Palisading granuloma may convert to giant cell nodule or micronodular scar. Interstitial fibrosis is common, and pneumonitis resembling usual interstitial pneumonitis can develop. If only healing or residual disease is encountered, one should search further clinically and pathologically for active disease. Dampened inflammatory lesions represent smoldering disease that presumably needs additional therapy. Scarring presumably represents successfully treated but permanent disease.

Adult↗
PubMed1997

Primary alveolar soft-part sarcoma of the mediastinum: a clinicopathological and immunohistochemical study of two cases.

AIMS: Primary alveolar soft part sarcomas originating within the thoracic cavity are rare. The cases herein described highlight the ubiquitous distribution of this neoplasm and the importance of considering this tumour in the differential diagnosis of mediastinal tumours. METHODS AND RESULTS: Two cases of alveolar soft-part sarcoma of the mediastinum are presented. The patients are two men of 22 and 23 years of age. Clinically, the patients presented with symptoms of chest pain. One tumour was in the anterior mediastinum while the second tumour was in the posterior mediastinum. Even though the bulk of the tumours were in mediastinal locations, both patients had pulmonary metastases at the time of diagnosis. Histologically, both tumours showed the classic morphology of alveolar soft part sarcoma, i.e. a proliferation of large polygonal cells with round to oval nuclei, prominent nucleoli and moderate amounts of eosinophilic cytoplasm arranged in a prominent alveolar pattern. Periodic acid-Schiff stains showed the characteristic diastase-resistant intracytoplasmic crystals. Immunohistochemical studies showed focal myoglobin reactivity in one case, while cytokeratin, vimentin, S100 protein, chromogranin, synaptophysin, neurofilaments, leu-enkephalin, desmin, smooth muscle actin and muscle-specific actin were negative in both cases. The patient with the anterior mediastinal tumour died of disease 14 months after diagnosis, and the patient with the posterior mediastinal mass remained well for at least 15 years and was later lost to follow-up. CONCLUSIONS: As has been observed in other anatomic areas, namely soft tissues, alveolar soft part sarcomas may follow an uncertain natural history. Interestingly, in our cases, the tumour in the anterior mediastinum followed a fatal course raising the possibility that the anatomic location of the tumour may have play a role in the behaviour of the tumour.

Adult↗
PubMed1997

Clear cell "sugar" tumor of the lung: association with lymphangioleiomyomatosis and multifocal micronodular pneumocyte hyperplasia in a patient with tuberous sclerosis.

We report the unique association of a clear cell "sugar" tumor of the lung (CCTL) in a 32-year-old woman with tuberous sclerosis (TSC), lymphangioleiomyomatosis (LAM), and multifocal micronodular pneumocyte hyperplasia (MMPH). Chest radiographs demonstrated a peripheral solitary 1.0-cm lingular nodule, diffuse emphysematous changes, and bilateral pneumothorax. Microscopic examination of the coin lesion showed an unencapsulated tumor composed of round to oval to focally spindled cells with distinct cellular borders, abundant clear to eosinophilic granular cytoplasm, prominent thin-walled blood channels, and focal hyaline stroma. Rare multinucleated cells were identified, and neither necrosis nor mitotic figures were seen. Tumor cells contained abundant diastase-sensitive intracytoplasmic glycogen, as demonstrated with periodic acid-Schiff stains. Tumor cell immunoreactivity for HMB-45 and nonreactivity for cytokeratin supported the diagnosis. The lung tissue also contained MMPH and smooth muscle proliferations diagnostic of LAM. The histogenesis of CCTL remains controversial, and similarities between this lesion and both LAM and angiomyolipoma (AML) raise the possibility that these lesions are related not only to each other, but that CCTL should be added to the spectrum of pulmonary manifestations of TSC.

Adenocarcinoma, Clear Cell↗