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S D Greenberg

Publications and source records attributed to S D Greenberg.

At least 19 recordsLinked to original sources

Absence of correlation between nuclear morphometry and survival in stage I non-small cell lung carcinoma.

To evaluate the utility of nuclear morphometry as a prognostic indicator in lung cancer, 5-year follow-up information was obtained in 46 cases of surgically resected Stage I non-small cell lung cancer (NSCLC). Nuclear area, perimeter, major diameter, minor diameter, and nuclear shape factor were determined from representative histologic sections of the tumors with a computer-assisted digitizing system. The morphometric parameters were compared between patients with favorable outcome (Group I: alive with no evidence of disease, n = 17) and those with poor outcome (Group II: dead of disease or with recurrence of disease, n = 29). No significant differences in any of the morphometric parameters were found between tumors in Groups I and II for individual tumor cell types or the combined cases. Failure to demonstrate a correlation between morphometric parameters and prognosis in Stage I NSCLC indicates that future efforts to determine objective prognostic factors should concentrate on other variables, such as specific genetic abnormalities.

Aged

Prognostic significance of histopathologic subtype and stage in small cell lung cancer.

A study of 149 light microscopic tissue slides from 147 patients with recorded initial diagnoses of small cell lung cancer (SCLC) (114 cases) and undifferentiated carcinoma (35 cases) was undertaken to test the reproducibility and prognostic impact of a new histopathologic subclassification of SCLC proposed by the Pathology Panel of the International Association for the Study of Lung Cancer (IASLC). This study was further designed to test the impact of clinical stage, age, sex, and race on survival. The tissue slides were blindly reclassified as SCLC or non-SCLC by a panel of five pathologists with no knowledge of the initial diagnosis. The SCLCs were divided into the three subtypes outlined by the IASLC pathology panel: small (classic or pure), mixed (small cell/large cell), and combined (small cell/squamous carcinoma or small cell/adenocarcinoma). Small cell lung cancer was clinically staged as local, regional, or distant. Consensus diagnosis (defined as agreement by at least three of the five pathologists) was achieved in 144 (96.6%) of the 149 cases. Of these 144 cases, 124 were reclassified as SCLC (115 [92.8%] small, five [4.0%] mixed, and four [3.2%] combined) and 20 were classified as non-SCLC. The median lengths of survival for the small, mixed, and combined subtypes were 225, 1,110, and 203 days, respectively (P = .025). Adequate staging data were available in 123 of the 124 SCLC cases. Of the 123 SCLC cases, 27 (21.9%) were local, 22 (17.9%) were regional, and 74 (60.2%) were distant stage. The median lengths of survival for the local, regional, and distant stages were 428, 251, and 111 days, respectively. This association was highly significant (P = .0001). We conclude that stage is the major determinant of survival in SCLC. Mixed subtypes had significantly longer survival times than the small or combined subtypes (P = .025). Survival times were longer for women than for men, and the survival time difference between men and women was significant (P = .0028). We found no significant differences in survival according to age or race.

Carcinoma, Small Cell

Aspiration injury due to polyacrylamide.

Acute lung injury secondary to aspiration of polyacrylamide, a synthetic polymer used widely in industry, has not been previously described in man or animal. We report the case of a 26-year-old man who aspirated polyacrylamide gel while cleaning it out of a tank truck. Subsequently, severe airway obstruction and lung parenchymal damage developed, and the patient died. At autopsy, numerous polyacrylamide particles were found in the lungs, along with extensive bronchiolar and alveolar damage.

Accidents, Occupational

Transbronchial lung biopsy. Histopathologic and morphometric assessment of diagnostic utility.

The diagnostic utility of transbronchial lung biopsy (TBB) is partly a function of its size. However, objective parameters that reflect biopsy specimen size have not yet been well-defined. We studied clinical records and histopathologic lung tissue slides of 116 patients who underwent diagnostic TBB, aiming to define the possible significance of association between seven parameters and three categories of pathologic diagnoses. Three of the seven parameters were clinical: age, sex, and chest roentgenographic infiltrates (localized vs diffuse). The remaining four parameters were histopathologic and morphometric: total number of tissue fragments, total number of alveoli (per biopsy specimen), total tissue area (alveolated plus nonalveolated), and lung total area (alveolated tissue alone). The three categories of pathologic diagnoses were as follows: infection, tumor, and nonspecific diagnoses. The nonspecific diagnoses included diagnoses of fibrosis and/or chronic inflammation. The alveoli were microscopically counted by one of us (S.D.G.). The number of biopsy fragments, the total tissue area, and the total lung area were measured in square millimeters by a computer-assisted digitizing system using specific (Bio-Quant) software (R and M Biometrics Inc). The significance of the associations between the seven parameters and the three diagnostic categories were assessed by the chi2 test for association. Overall, the following four possible associations were found to be statistically significant: (1) age--a lower percentage of patients with infection was found among patients with increasing age (p less than 0.001); (2) roentgenographic findings--a greater percentage of tumor diagnoses were found in patients with localized infiltrates (p = 0.006); (3) number of biopsy fragments--a greater percentage of patients with diagnoses of infection was identified among patients whose biopsy specimens contained the highest number of tissue fragments (p = 0.04); and (4) number of alveoli--a greater percentage of diagnosis of infection was made in patients whose biopsy specimens contained greater than or equal to 20 alveoli (p = 0.01). Our findings support the notion that the diagnostic utility of TBB is related to its size. However, this relationship between TBB size and diagnostic utility was apparent only for diagnoses of infection and not for diagnoses of tumor. We conclude that TBB specimens containing 20 or more alveoli may (1) be declared to be adequate for diagnosis, (2) in the appropriate clinical setting, they will be most likely to yield a diagnosis of infection, and (3) the number of alveoli does not appear to be associated to the diagnosis of tumor.

Biopsy

Experimental polyacrylamide-induced acute injury in rat lung.

We recently reported the first case of accidental aspiration of polyacrylamide occurring in a 26-year-old man. The patient developed severe airway obstruction and parenchymal lung damage and died. Autopsy revealed numerous polyacrylamide particles in his lungs, as well as extensive bronchiolar and alveolar damage. Gas chromatographic and mass spectrometric assessment of the lung tissue failed to reveal polyacrylamide activity, although assessment of the suspending solvent of the polyacrylamide showed a pattern characteristic of an aliphatic hydrocarbon mixture with a prominent dodecane peak. This experimental study was performed to determine the nature and extent of damage to rat bronchial and alveolar epithelia following endotracheal instillation of polyacrylamide, hydrocarbon mixture (petroleum distillate), dodecane (C12H26), or normal saline. The rat lungs were examined grossly and microscopically 10 min and 24, 72, and 96 h after endotracheal instillation, following inflation and fixation with 10 percent buffered formaldehyde. Gross examination revealed congested, mottled visceral pleural surfaces in the rats treated with polyacrylamide and dodecane. There were no pleural exudates or effusions. Microscopically, vascular engorgement, bronchiolitis, and focal pneumonia were observed. Vascular engorgement was most pronounced at 72 to 96 h in rat lungs treated with polyacrylamide and dodecane and was moderate at 24 h in rats treated with petroleum distillate. Focal organizing pneumonia was marked at 96 h in rats treated with petroleum distillate, at 72 h in those treated with polyacrylamide, and at 24 h in those treated with dodecane. The saline-treated control animals showed no change. Our findings suggest that polyacrylamide, dodecane, and petroleum distillate are strong irritants to the airways. However, a direct obstructive/mechanical effect of the polyacrylamide upon the airway has not been excluded. Airway exposure to polyacrylamide may result in lung injury secondary to the polyacrylamide itself, its suspending agents, or both.

Acrylic Resins

Heart allograft involvement with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder.

We describe a 60-year-old man who underwent heart transplant and died 5 months later. At autopsy, the patient was found to have posttransplant lymphoproliferative disorder (PTLD), which was not suspected ante mortem. The PTLD involved the lung, lymph nodes, spleen, and kidney and the intima of right coronary artery of the transplanted heart. Epstein-Barr virus infection was demonstrated on direct gel and dot blot after polymerase chain reaction amplification. In situ hybridization for Epstein-Barr virus DNA confirmed the presence of Epstein-Barr virus-infected lymphocytes in the intima of the right coronary artery of the cardiac allograft. To our knowledge, this case represents the first report of involvement of a heart allograft by PTLD in which Epstein-Barr virus infection of the atypical cells is documented. Although primary allograft involvement by PTLD has rarely been reported in heart transplant recipients, recognition that this may occur is important, since the lymphoid infiltrate of PTLD must be distinguished from the lymphoid infiltrate of acute rejection to avoid inappropriate therapy.

Base Sequence

Morphometric quantitation of tumor necrosis in stage 1 non-small cell carcinoma of lung: prognostic implications.

We objectively examined the extent of tumor necrosis by computer-assisted morphometry in 28 patients with surgically resected Stage I non-small cell carcinoma of lung. Fourteen of the 28 patients were long-term survivors (mean survival after diagnosis 94 mo) and 14 were short-term survivors (up to 62 mo after diagnosis). The extent of tumor necrosis was determined by means of a computer assisted digitizing system. The two sample t test and the two-tailed Wilcoxon rank score tests were used for statistical analysis of comparison of the extent of tumor necrosis between the two groups of patients. This morphometric study showed that the extent of tumor necrosis was significantly associated to the probability of long-term survival, with long surviving patients having a lesser degree of tumor necrosis (t = 2.75, p < 0.02, 2 sample t test, two-tailed, df = 26). These findings reaffirm previous subjective data, derived from pathologist assessment of tumor necrosis, and suggest that morphometric evaluation of tumor necrosis may play a useful adjunct role in predicting prognosis of carcinoma of lung.

Carcinoma, Non-Small-Cell Lung

Carcinoma of the larynx. Changing incidence in women.

Laryngeal carcinoma has classically been considered a disease of men with a history of tobacco and alcohol abuse. Substantial increases in the incidence of laryngeal carcinoma have occurred among both men and women from 1947 through 1984. In men, the incidence has increased from 5.6 to 9.0 per 100,000 population and in women, from 0.5 to 1.5 per 100,000 population. We recently encountered three consecutive cases of laryngeal carcinoma in women at the Ben Taub General Hospital, Houston, Tex, diagnosed and treated over a 3-month period. Each woman had a long history of cigarette smoking, and two also had a history of alcohol abuse. These consecutive presentations of laryngeal carcinomas in women prompted us to examine our Cancer Registry Files from 1959 through 1973 and 1974 through 1988. Over these two 15-year periods, the male-to-female ratio declined from 5.6:1 to 4.5:1, reflecting a greater incidence among women.

Adult

Changing utilization of cytopathology versus histopathology in the diagnosis of lung cancer.

We studied the utilization rates of 1) cytopathology procedures [sputum, fine-needle aspirates (FNA), bronchial washings and brushings] versus 2) histopathology procedures (bronchial biopsies, lymph node biopsies, lobectomies, pneumonectomies) in the diagnosis of lung cancer, over two time periods (1967/1987). Comparisons were made in the utilization rates of these two diagnostic procedures in two groups of 100 patients each. Statistically significant changes included 1) an increase of cytopathology procedures, as the sole means of diagnosis; 2) an increase in FNAs; 3) an increased percentage of positive cytopathologic diagnosis; and 4) a decrease of major surgical procedures (lobectomy, pneumonectomy), as means of initial pathologic diagnosis. This study provides data supporting the trend of decreasing surgical procedures for initial diagnosis of lung cancer, with greater, more effective utilization of cytopathologic (particularly FNA) procedures.

Cytodiagnosis

Diagnosis of diffuse malignant mesothelioma: experience of a US/Canadian Mesothelioma Panel.

The experience of the US/Canadian Mesothelioma Panel with its first 200 cases is reviewed. The light microscopic diagnosis, histochemical findings, immunohistochemical findings, and electron microscopic features of malignant mesotheliomas are reviewed in the context of differential diagnosis. Reasons for referral of case material to the panel and lessons from follow-up of difficult and controversial cases are reported. Recommendations to general pathologists are made regarding evaluation and review of possible mesotheliomas.

Adenocarcinoma

Lymphocyte subset populations in bronchiolitis obliterans after heart-lung transplantation.

The long-term success of heart-lung transplantation is limited by the development of bronchiolitis obliterans, possibly as a form of chronic lung allograft rejection. In the present study, we have characterized by immunohistochemical staining the lymphocytes infiltrating the lesions of bronchiolitis obliterans in one patient following heart-lung transplantation. The finding that the preponderant cells expressed the CD8 (putative cytotoxic/suppressor) marker lends support to the notion that chronic rejection is at least one mechanism for the development of bronchiolotis obliterans following heart-lung transplantation.

Adult

Morphology of bronchial epithelium adjacent to adenocarcinoma of the lung.

Gross unremarkable bronchi and bronchioles from 22 lobectomy specimens containing primary adenocarcinoma were examined microscopically. Sections were taken from the segment containing the carcinoma and compared with sections taken from uninvolved segments in the same specimen to examine for premalignant lesions. The average tumor size was 3.75 cm (1.5 to 11 cm). The average age of patients was 60.4 yr (29 to 79 yr); 13 were men and nine were women; all were smokers, and the average was 44.1 pack-years (20 to 100 pack-years). Six of the specimens (27%) showed no histologic changes. Focal squamous metaplasia was identified in nine specimens (41%), but in four of the nine (44%), it was not seen in the carcinogenic segment. Focal goblet cell metaplasia was seen in six specimens (27%), but in two of the six (33%), it was not in the carcinogenic segment. Focal basal cell hyperplasia was seen in two specimens (9%) within both the carcinogenic segment and elsewhere. A single focus of mild epithelial dysplasia was found in each of two specimens (9%), but these foci were not in the carcinogenic segment. Focal epithelial regeneration was noted in three specimens (14%), but two of these (66) were not in the carcinogenic segment. Such microscopic abnormalities of respiratory epithelium are associated with cigarette smoking, and each is a potentially premalignant change; however, our study demonstrated no histologically identifiable changes in the respiratory epithelium that consistently mark for premalignant atypia in the lung adenocarcinoma.

Adenocarcinoma

Immunohistochemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms.

A sizable proportion of pleural malignant mesotheliomas are sarcomatoid (22%) or biphasic (24%) and may need to be distinguished from other spindle cell neoplasms that occur as primary or metastatic tumors of the chest wall or lungs. To determine the utility of immunohistochemistry in the differentiation of sarcomatoid malignant mesotheliomas from other spindle cell neoplasms, the authors studied the immunostaining patterns of nine antibodies in four sarcomatoid mesotheliomas, one desmoplastic mesothelioma, two epithelial mesotheliomas, four spindle cell squamous carcinomas, and eight sarcomas of various differentiation. Three of the four sarcomatoid mesotheliomas and the desmoplastic mesothelioma had positive results for cytokeratin, which distinguishes them from sarcomas but not from spindle cell squamous carcinomas. The immunostaining pattern of 14 examples of benign spindle cell mesothelial proliferation was similar to that of the sarcomatoid mesotheliomas, which supports the theory that these tumors are mesothelial in origin. Although other antibodies occasionally may be helpful, depending on the differentiation of the sarcoma, cytokeratin immunostaining appears to be the best method to discriminate sarcomatoid mesotheliomas from sarcomas.

Aged

Cytomorphometry of large cell carcinoma of the lung.

A computerized morphometry system was used to evaluate criteria for the cytologic diagnosis of large cell carcinoma (LCC) and poorly differentiated adenocarcinoma of the lung. There were 143 cells measured in six cases of LCC (five sputums and one bronchial washing) and 61 cells in four cases of adenocarcinoma (all sputum samples). Cellular and nuclear areas were significantly larger in adenocarcinoma whereas nucleolar area was greater in LCC, producing a higher nucleolar/nuclear area ratio in LCC. Cellular and nuclear form factors were smaller in LCC while the minor axis was longer in adenocarcinoma, resulting in a smaller axial ratio in adenocarcinoma. These data indicate that adenocarcinoma cells are larger and have a more rounded shape and less nucleolar material, as compared to the smaller, more ellipsoid and convoluted cells of LCC, which have more nucleolar area. A logistic regression identified cellular area, nucleolar/nuclear area ratio and cellular and nuclear form factors as significant contributors to the discrimination of LCC from adenocarcinoma, with a positive predictive value of 92%. Morphometry may therefore be helpful in the differential cytologic diagnosis of adenocarcinoma and LCC.

Adenocarcinoma

Immunohistochemical diagnosis of pulmonary eosinophilic granuloma on lung biopsy.

S-100 protein immunostaining has been advocated to identify the characteristic Langerhans' cells in the histologic diagnosis of PEG. Reliable demonstration of an increased number of Langerhans' cells is essential in difficult biopsy cases, since occasional Langerhans' cells can be found in other pulmonary lesions. We examined the S-100 protein labeling pattern in three cases of PEG and in a variety of controls. Non-Langerhans' histiocytes were labeled for lysozyme antigen on the same histologic sections using a combined ABC and PAP technique. This verified that the S-100 protein-negative histiocytes were indeed a separate population from the S-100 protein-positive histiocytes and did not represent Langerhans' cells which failed to label with antiserum to S-100 protein. This technique confirms the usefulness of S-100 protein staining in the diagnosis of PEG and offers a means to verify the reliability of the S-100 protein labeling in questionable cases.

Biopsy

Differences in lectin binding of malignant pleural mesothelioma and adenocarcinoma of the lung.

In order to differentiate between malignant pleural mesothelioma and adenocarcinoma of the lung, the glycoconjugate profiles of 6 reactive mesothelial lesions, 23 mesotheliomas (17 epithelial, 1 desmoplastic, 2 biphasic, and 3 fibrous types), and 28 well-differentiated pulmonary adenocarcinomas were evaluated with the use of 8 lectins in addition to anti-carcinoembryonic, anti-keratin and anti-epithelial membrane antigen. Formalin-fixed, paraffin-embedded tissues were stained with the avidin-biotin peroxidase complex method. Reactions of wheat germ (WGA) and peanut (PNA) agglutinin with neuraminidase treatment lectins were positive in 5 of 6 (83%) and 3 of 6 (50%) cases, respectively, in reactive mesothelial lesions. Thirteen of 23 (57%) malignant mesotheliomas of the pleura showed a positive reaction for WGA and PNA with neuraminidase treatment; other lectins were low-positive, below 9%. In contrast, pulmonary adenocarcinomas showed positive reactions in 27 of 28 cases (96%) for PNA, 26 of 28 (93%) for Ricinus communis (RCA-I), 25 of 28 (89%) for WGA, and 22 of 28 (79%) for succinylated WGA (SucWGA). The findings suggest that malignant pleural mesothelioma and pulmonary adenocarcinoma have consistent and distinct glycoconjugate profiles, and that stains for RCA-I and SucWGA may be useful for differential diagnosis.

Adenocarcinoma