Merkle cell carcinoma report of a case and possible role for adjuvant radiotherapy.

A case of neuroendocrine (Merkle cell) carcinoma of the skin is described. This uncommon tumor occurred in a 76-year-old female and presented as a small exophytic nodule on the right anterior chest wall. Following primary excision, it was thought to be a basal cell carcinoma. The diagnosis of Merkle cell carcinoma was established only after the tumor had recurred locally and involved ipsilateral axillary lymph nodes. Although local control was achieved with surgery and radiotherapy, the patient died of probable hepatic metastases 18 months after presentation. The Merkle cell tumor is an undifferentiated small cell carcinoma originating in the skin and has distinct ultrastructural characteristics that help to differentiate it from other small cell tumors. The clinicopathologic characteristics of these potentially aggressive neoplasms are reviewed, and treatment is briefly discussed.

Pathogenesis of acute Legionnaires' disease pneumonia.

Immunofluorescent study of the lungs in cases of fatal suspected acute Legionnaires' disease enabled confirmation of the presence of Legionella pneumophila. In addition, probable pathogenetic mechanisms that had not been as clearly visualized by light microscopy became apparent: the retrograde involvement of the larger bronchioles and proximal airways, invasion of the interstitium, extension to pleura, and lymphatic and hematogenous spread. Organisms were demonstrated to occur in the liver and spleen of one patient. The development of technics for the earliest possible diagnostic verification of Legionnaires' disease, with specimens obtained as untraumatically as practical from selected sites and screened by specific immunofluorescent microscopic examination, should contribute to patient survival.

A Legionella-like bacterium related to WIGA in a fatal case of pneumonia.

An unusual bacterium serologically related to a "rickettsia-like agent," designated previously as WIGA, was seen in lung tissue from a patient who died of pneumonia of unknown cause. A fluorescent antibody conjugate prepared with the WIGA organism, isolated in 1959, was used to stain the lung tissue. Enormous numbers of fluorescent bacteria in the lungs of this patient confirm the pathogenicity of this unusual bacterium.

Pathologic findings and long-term sequelae in Legionnaires' disease.

A recently recognized sporadic case of Legionnaires' disease occurring in North Carolina is described. Diagnosis was made by special serologic studies performed at the Center for Disease Control, Atlanta. The light-microscopic and electron-microscopic findings are described. Organisms consistent with the etiologic agents of Legionnaires' disease were seen by electron microscopic examination. An eight-month follow-up in this case still showed the presence of some radiologic abnormalities of the pulmonary parynchema, as well as abnormal data on tests of pulmonary function.

Ultrastructure of the Legionnaires' disease bacterium. A study using transmission electron microscopy.

The Legionnaires' disease (LD) bacterium appeared ultrastructurally identical in human lung, egg yolk membrane, and artificial media, seen as a blunt or tapering rod measuring 0.3 to 0.9 micron in diameter and greater than or equal to 2.0 micron long. Greatly elongated forms were commonly found in cultures and yold sac membranes after 5 to 7 days of growth but were only rarely seen in human lung. The LD bacterium was clearly prokaryotic. Prominent features included electron-lucent nucleoids interspersed among areas of well-defined ribosomes; cleanly circumscribed cytoplasmic vacuoles or granular inclusions; and a double envelope enclosure, each portion consisting of a triple-layered "unit" membrane, approximately 75 A wide. Division always occurred as a pinching, nonseptate process typical of bacteria with a double, gram-negative type of envelope. No definite structure was seen in the periplasmic space that might represent the peptidoglycan layer. These features of the LD bacterium confirm earlier reports of the gram-negative staining reaction of organisms obtained from cultures and preliminary evidence of their gram-negative ultrastructure. We found no unique features that would aid in the ultrastructural differentiation of the LD bacterium from other small gram-negative bacilli.

Pathologic findings in guinea pigs inoculated intraperitoneally with the Legionnaires' disease bacterium.

Tissues from guinea pigs inoculated intraperitoneally with the Legionnaires' disease (LD) bacterium were studied with light, immunofluorescent, and electron microscopy. The principal gross lesion was diffuse peritonitis of varying severity. Microscopically, the peritonitis of covered by a mixed inflammatory infiltrate of macrophages, neutrophils, fibrin, and cellular debris. Foci of inflammation and necrosis were consistently observed in the splenic parenchyma, and similar lesions were often found in the lungs, liver, lymph nodes, pancreas, heart, and other organs. Numerous LD bacteria were seen in the peritoneal exudate; fewer were found in disseminated lesions. In electron micrographs, the highest concentrations were seen in macrophages, with fewer organisms present in neutrophils or extracellular spaces. Although the lung is the primary organ konwn to be affected by Legionnaires' disease in humans, our findings indicate that the LD bacterium is capable of dissemination.

Pulmonary sequelae of acute Legionnaires' disease pneumonia.

Patients with acute Legionnaires' disease (LD) pneumonia may have persistent chronic pulmonary changes, as shown by the histologic appearance of specimens of lung from patients who had survived and autopsy specimens from patients who died after a protracted clinical course. Acute pneumonia was not seen in these lungs, and LD organisms could not be identified by the direct fluorescent antibody technique or the Dieterle silver impregnation strain; instead, there was organizing pneumonia with various degrees of interstitial inflammation and fibrosis. The LD pneumonia may fail to resolve, and the lung parenchyma in areas of previous acute inflammation is not restored to normal in some patients.

Ultrastructure of the agent of Legionnaires' disease in the human lung.

This report confirms the gram-negative ultrastructural characteristics of the Legionnaires' disease organism by direct examination of pulmonary tissue from six confirmed cases--two from the original Philadelphia epidemic of 1976 and four from more recent sporadic cases. All microorganisms seen in all six lungs were identical ultrastructurally and were predominantely within intra-alveolar macrophages, as previously observed by light microscopy. They appeared as short, blunt rods that were clearly prokaryotic; i.e., they had diffuse electron-lucent nucleoid areas interspersed among areas of well-defined ribosomes, a pinching nonseptic division, and enclosure within a double envelope consisting of two three-layer "unit" membranes, each approximately 75 A wide. This structure, together with a pinching division, is typical of gram-negative bacteria. The Legionnaires' disease organism multiples both intracellularly and extracellularly in tissue and has no unique ultrastructural features that would aid in its specific identification. These findings are compared with recent reports describing the ultrastructure of what was considered to be the Legionnaires' disease organism in yolk sac and culture medium, and in one human lung.

Legionnaires' disease. Pathological and historical aspects of a 'new' disease.

Autopsy tissues and protocols from 26 epidemiologically defined fatal cases of Legionnaires' disease occurring during the 1976 Philadelphia outbreak were reviewed. Consistent pathologic features were limited to the lung, where an acute pneumonia characterized by intra-alveolar exudation of neutrophils, macrophages, and fibrin was observed. An etiologic agent common to most of the victims of Legionnaires' disease was identified within the pneumonic process by application of the Dieterle silver impregnation stain. In some cases, other pulmonary histologic findings were noted, chiefly acute diffuse alveolar damage. However, the importance of acute diffuse alveolar damage is not understood.

The emerging role of carcinodevelopmental antigens in the clinical laboratory.

Patterns of carcinoembryonic antigens (CEA) in fetal gut, seminal plasma, and amniotic fluids were investigated. In fetal gut the broadest range of CEA-expression occurred during the period of maximal mucosal differentiation. While normal adult colon or other fetal stages expressed lower quantitative and qualitative amounts of CEA, maximal CEA expression could be found in a pool of 20 primary adenocarcinomas of the colon. Low levels of CEA in seminal plasma were associated with subfertile, poorly differentiated sperm as opposed to CEA levels found in either normal ejaculates or those obtained from vasectomized, previously fertile males. In amniotic fluid CEA remained at a constant level between the 16th and 22nd week in utero as did fructose and urea levels. Glucose and histaminase levels showed great variance. The relationship of these latter findings to genetic defects is currently being investigated. These data suggest that an ever increasing number of biologic samples will be tested in the clinical laboratories for carcinodevelopmental antigen levels. These will be used for the prognosis and/or diagnosis of abnormal differentiation patterns in patients with cancer or in the developing fetus.