Gerald Nash

Immunoreactive neuron-specific enolase, bombesin, and chromogranin as markers for neuroendocrine lung tumors

Sixty-four lung tumors were evaluated for the presence of immunoreactive neuron-specific enolase (NSE), bombesin (Bn), and chromogranin (Cg) to assess their value as markers for neuroendocrine cells in the histologic diagnosis of pulmonary neoplasms. Staining was correlated with the presence and density of neurosecretory granules (number of neurosecretory granules per unit cytoplasmic cross-sectional area) as determined by planimetry on electron micrographs. The cytoplasmic density of neurosecretory granules was significantly greater in the carcinoid tumors than in the small cell carcinomas (P less than 0.001). Neuron-specific enolase was localized in all of the neuroendocrine granule-bearing tumors but was also present in 57 per cent of the nonneuroendocrine carcinomas. Bombesin was present in 68 per cent of the neuroendocrine tumors and in less than 1 per cent of the nonneuroendocrine tumors. Staining for Cg appeared to correlate with the density of neuroendocrine granules, with staining in carcinoid tumors but no staining in small cell anaplastic carcinomas. A panel of antibodies may be required for the reliable identification of neuroendocrine lung tumors by immunohistochemical techniques.

Keratin proteins and carcinoembryonic antigen in lung carcinoma: An immunoperoxidase study of fifty-four cases, with ultrastructural correlations

This study evaluates the use of immunoperoxidase stains for keratin and carcinoembryonic antigen (CEA) in the diagnosis of lung cancer. Immunohistochemical staining for these antigens was performed on paraffin sections from 54 lung neoplasms, and the results were correlated with the histologic, histochemical, and ultrastructural appearances of the tumors. Strong staining for keratin proteins was evident in all squamous cell carcinomas. This reaction was particularly helpful in identifying squamous differentiation in poorly differentiated areas and in cases in which tonofilaments appeared to be sparse or absent on electron microscopy. Weak focal staining for keratin was evident in only two cases of adenocarcinoma, and the difference in frequency of staining between squamous cell carcinomas and adenocarcinomas was statistically significant ( P =0.01). Carcinoembryonic antigen was variably present in all types of lung carcinoma, but staining for it was strongly positive in cases of adenocarcinoma. Positive staining for keratin with negative or focal weak staining for CEA was characteristic of mesotheliomas, which was helpful in differentiating them from adenocarcinomas. When evaluated by multiple means including immunohistochemical analysis, tumors with mixed differentiation were frequently identified and most large cell carcinomas showed evidence of glandular or squamous differentiation. Electron microscopic demonstration of neurosecretory granules was the best single diagnostic criterion for small cell anaplastic carcinomas ( P =0.01, as determined by stepwise logistic regression analysis). Also helpful in differentiating between small and large cell anaplastic carcinomas were a significantly smaller mean cell diameter in the former, as measured on electron micrographs ( P =0.05), and positive staining for keratin, which occurred significantly more often in large cell carcinomas ( P =0.03). These findings suggest that immunoperoxidase stains for keratin and CEA supplement routine histochemical and electron microscopic studies in the diagnosis of lung tumors, and may provide additional specific objective criteria for their classification.

Herpetic esophagitis. A common cause of esophageal ulceration.

Abstract Although herpetic esophagitis is generally believed to be rare, a microscopic study of 55 cases of esophagitis encountered in a review of autopsies revealed 14 cases (approximately 25 per cent). The pathology of herpes esophagitis is described and reasons it has been overlooked are discussed. Possible predisposing factors include immunosuppressive therapy and trauma from nasogastric intubation. Herpetic esophagitis was clinically significant in only one patient, but four patients also had herpes pneumonia, a life threatening infection that occurs concomitantly with esophageal involvement. This association should be kept in mind when herpetic esophageal ulcers are observed at autopsy.

Localized fibrous mesothelioma: An immunohistochemical and electron microscopic study

The absence of keratin staining in tumor cells from localized fibrous mesotheliomas in both paraffin-embedded and frozen sections with sensitive peroxidase-antiperoxidase and avidin-biotin techniques is described. In addition ot the absence of staining for whole-stratum corneum keratin proteins, sections were negative for keratins of different molecular weights (45, 55, and 63 kilodaltons) that are characteristically present in mesothelial cells. Ultrastructurally, the cells most closely resembled mesenchymal cells of the fibroblastic type. These findings are in accordance with recent theories that relate the derivation of localized fibrous mesotheliomas to nonmesothelial cells, including subpleural connective tissue. Based on differences in immunohistochemical staining, the tumors appear to be unrelated to diffuse malignant mesotheliomas.

Pulmonary interstitial edema and hyaline membranes in adult burn patients: Electron microscopic observations

Abstract Pulmonary insufficiency has become a major problem in the care of patients with extensive cutaneous burns and other forms of trauma. Although a variety of pathological changes have been described in the lungs of such patients, probably the most common underlying lesion is interstitial edema with the development of hyaline membranes. Previous light microscopic investigations have shown that interstitial edema with hyaline membrane development is a nonspecific pulmonary reaction that occurs in many conditions and in response to a variety of stimuli. In this study, postmortem electron microscopic observations on the lungs of six burn patients with the lesion are described. Interstitial edema of the alveolar wall was marked and involved primarily the thick portion of the air-blood membrane. The thin portion of the membrane, where epithelial and endothelial basement membranes are normally in close proximity, did not demonstrate accumulation of edema fluid. There was widespread necrosis of the alveolar epithelium. Cellular debris from necrotic alveolar epithelium and fibrin-like material formed a layer that corresponded to the hyaline membranes observed by light microscopy. Hyaline membranes occurred both with and without edema of the underlying interstitium, seemingly indicating that interstitial edema per se was not solely responsible for the epithelial necrosis and resulting hyaline membranes. Evidence of alveolar epithelial regeneration was also found. The regenerated cells had the appearance of type II alveolar cells (granular pneumocytes), which are thought to be the reserve cells of the alveolus. Changes in the alveolar capillaries were minimal. This was a surprising finding, since changes in the interstitium suggested an altered capillary permeability. However, the possibility that endothelial injury had occurred early in our patients and was repaired by the time of their demise could not be ruled out. Futher ultrastructural studies are needed to describe the sequential development of the lesion and to compare the trauma-related lesion with the interstitial edema-hyaline membrane pattern in other clinical and experimental settings.

Immunoperoxidase localization of keratin proteins, carcinoembryonic antigen, and factor VIII in adenomatoid tumors: Evidence for a Mesothelial Derivation

The histogenesis of adenomatoid tumors has been a source of controversy. Although most investigators favor a mesothelial derivation, recent ultrastructural evidence suggests that some adenomatoid tumors may be vascular neoplasms. This study reports the pattern of staining of seven adenomatoid tumors with antisera to keratin, factor VIII, and carcinoembryonic antigen (CEA), using an immunoperoxidase technique. All the tumors revealed strong cytoplasmic staining for keratin with no staining for factor VIII (an endothelial cell marker) or CEA. An identical staining pattern was evident in normal and reactive mesothelial cells. These findings support a mesothelial rather than an endothelial derivation for the tumors studied.

Pathologic features of the lung in the immunocompromised host.

Acute pulmonary disease is a major complication of immunodeficiency, and it has become increasingly important with the expanded use of immunosuppressive drugs. When routine clinical evaluation fails to identify a specific etiologic agent, a morphologic diagnosis is pursued by means of one or more invasive procedures. Interpretation of the material obtained by these procedures poses a challenge to pathologists. In this paper, the important histopathologic patterns of pulmonary disease likely to be encountered in this setting are reviewed, with emphasis on differential diagnosis. In addition, various diagnostic techniques are discussed and compared, with regard to interpretation of findings and diagnostic yields.

Kaposi's sarcoma presenting as pulmonary disease in the acquired immunodeficiency syndrome: Diagnosis by lung biopsy

Kaposis sarcoma frequently develops in patients with the acquired immunodeficiency syndrome (AIDS), and in most cases cutaneous lesions herald the disease. Although the lungs are often involved when the neoplasm becomes disseminated, it is rare for the initial diagnosis to be made by lung biopsy. This report describes two patients with AIDS in whom Kaposis sarcoma was present in lung biopsy specimens and in whom there was no other systemic evidence of the neoplasm. Both patients experienced hemoptysis, and pulmonary hemorrhage accompanied the neoplasm in each case. Only five microscopic foci of tumor were found in a total of 44 sections of lung examined. The focal distribution of the lesions in the pulmonary interstitium and the presence of coexisting lung disease posed problems in the evaluation of the biopsies. Awareness of the appearances of Kaposis sarcoma in lung tissue is important because the neoplasm will probably be encountered in lung biopsies with increasing frequency as more cases of AIDS are discovered.

Involucrin in intraepithelial and invasive squamous cell carcinomas of the cervix: An immunohistochemical study

Immunohistochemical staining for involucrin, a cytoplasmic protein synthesized during squamous maturation, was assessed in histologic sections from hysterectomy and cone biopsy specimens from patients with cervical neoplasia. In normal and condylomatous squamous epithelium, diffuse cytoplasmic staining was seen in the suprabasal layers, with no staining of the basal cells. Staining was absent in two cases of cervical intraepithelial neoplasia (CIN), grade III, in which the lesions were composed entirely of undifferentiated cells and markedly decreased in cases involving large numbers of basal cells. In 19 of 23 cases (83 per cent) of CIN, however, focal staining for involucrin was seen in large differentiated cells in the more superficial layers, and in two cases of keratinized CIN diffuse suprabasal staining was observed. Similarly, strong staining for involucrin was present in differentiated areas in one case of microinvasive squamous cell carcinoma and in 93 per cent of cases of infiltrating squamous cell carcinoma. These findings suggest that involucrin is a marker for maturation in cervical squamous epithelial neoplasms. Patterns of immunohistochemical staining for involucrin in keratinized dysplasia and differentiated squamous carcinomas should be taken into consideration if loss of involucrin staining is used as a criterion for neoplastic transformation of cervical epithelium, as has been proposed.