Type II pneumocytes in mixed cell culture of human lung: a light and electron microscopic study.

Alveolar Type II epithelial cells dedifferentiate rapidly in vitro. Studies with animal tissue suggest that cell-cell and extracellular matrix-cell interactions are important in the retention of Type II cell morphology in vitro. Thus, in this study with human tissue, alveolar Type II cells, alveolar macrophages, and spindle cells were prepared from the same sample of lung (obtained following lobectomy for cancer, n = 3), cocultured on glass cover slips or tissue culture plastic, and studied by light microscopy with scanning (SEM) and transmission (TEM) electron microscopy for 8 days. The primary cell isolates contained approximately 45% Type II cells; the remainder were macrophages or unidentifiable cells. Clusters, made up of a single layer of cuboidal Type II cells around a central core of connective tissue (largely collagen and some elastic tissue), formed above a monolayer of spindle cells. The Type II cells were morphologically similar to those seen in vivo. The cells were still cuboidal at 8 days but had lost their lamellar bodies, which were released into the medium via the apical surface. The clusters increased in size with time (area, microns 2: day 1, 29(5-143) x 10(2); day 8, 63(10-311) x 10(2); mean(range); p less than 0.02) without changing in number per culture, suggesting Type II cell proliferation. This may have been due to factors produced by the other cells and adherence to the extracellular matrix (ECM); (free collagen fibers, present in the original preparation, spindle cells, and/or Type II cells could be responsible for presence of ECM). We propose this as a useful model for the study of human Type II epithelial cells in vitro.

Duodenal ultrastructure in patients with chronic renal failure with a comment on the incidence of Campylobacter pylori infection.

This study was aimed at identifying ultrastructural abnormalities that may be present in the duodenum of patients with chronic renal failure who were undergoing hemodialysis and that may have an effect on the normal absorptive function of the duodenum. Duodenal biopsy specimens from ten patients and four controls were examined. Light microscopy showed gastric metaplasia in eight patients and in none of the controls. The main electron microscopic findings were related to the metaplastic changes, with abundant mucous globules and abnormal microvilli being seen in the affected columnar cells. Prominent lysosomes and wide intercellular spaces were seen in some areas. Goblet and enterochromaffin cells appeared to be normal. Some of the reported abnormal duodenal absorptive functions may be related to the ultrastructural abnormalities seen in the microvilli and the apical parts of the columnar cells. Because of the known association between gastric metaplasia and colonization of the duodenum with Campylobacter pylori, we looked for these organisms in our cases. Light microscopy demonstrated these bacteria in only one of the eight duodenal biopsy specimens with gastric metaplasia. Particles, probably representing degenerated bacteria, were seen by electron microscopy in most of the examined specimens, however, suggesting that the duodenum of these patients remains hostile to the growth of these organisms.

Mucinous carcinoma of the breast: further characterization of its three subtypes.

Nineteen cases of mucinous carcinoma of the breast were studied. Twelve tumours were of the pure type, and seven were mixed. All had abundant neutral and acidic mucin, and stained strongly with CAM 5.2. Of the 12 pure mucinous tumours, six were devoid of argyrophilic granules and were S-100 negative, and only one was CEA positive. All six patients are alive with no evidence of recurrence (mean follow-up 42 months). The other six pure mucinous tumours were rich in argyrophilic granules. Five of these showed S-100 positivity and all were CEA positive. One patient developed local recurrence and one died of myocardial infarction with no evidence of tumour recurrence (mean follow-up 80 months). Of the seven mixed tumours, only one contained an occasional cell with argyrophilic granules and four had variable degrees of CEA positivity. Two patients died and one developed bony metastasis (mean follow-up 40 months). Our findings emphasise the microscopic and prognostic differences between the three subtypes of mucinous carcinoma of the breast, and support the concept of dividing pure mucinous tumours into two distinct subtypes. We suggest that the latter subtyping can be qualitatively made on the basis of the presence or absence of argyrophilic granules in the tumour cells.

Liver cell carcinoma with orcein-positive granules and no identifiable copper.

A liver cell carcinoma removed surgically by partial hepatectomy from a 79-year-old woman contained abundant orcein-positive granules in many tumour cells. The granules were similar to those usually identified as representing copper-associated protein, yet they lacked copper, as demonstrated by negative rhodanine and rubeanic acid stains and energy dispersive X-ray microanalysis.

Cavernous haemangioma of breast in a man with contralateral gynaecomastia and a family history of breast carcinoma.

A 73-year-old man with a cavernous haemangioma of the right breast is presented. The patient had had gynaecomastia of the left breast 8 years earlier. Prior to that he had been on cimetidine for 2 years. The patient's mother and sister had breast carcinomas, while two other sisters and a brother had carcinomas of kidney, uterus and lung respectively.

Chronic intestinal pseudo-obstruction in two patients. Overlap of features of systemic sclerosis and visceral myopathy.

Two patients with chronic intestinal pseudo-obstruction are reported, one of whom had definite systemic sclerosis while the other had certain manifestations of the disease. Biopsies of the small intestine revealed increased collagen and elastic fibres in the muscularis propria and subserosa in each case, while ganglion cells were normal. In addition, one patient had severe atrophy of the inner muscle layer and the other obvious vacuolation of the muscularis propria. Ultrastructural examination confirmed degeneration of the smooth muscle fibres. These latter features have been considered the hallmark of visceral myopathy and their finding in this patient therefore suggests that the different causes of pseudo-obstruction may not be completely demarcated and cases in which the features overlap may occur.

Is neutrophil elastase associated with elastic tissue in emphysema?

To test the role of elastase in the pathogenesis of emphysema human neutrophil elastase (HNE) was localised by electron microscopy using an immunogold staining technique. Specific localisation of HNE to elastic tissue in emphysema did not occur, but non-specific binding of immunoglobulin G (IgG) to elastic tissue in emphysematous and normal lung tissue, which was completely blocked by the non-immune serum that was homologous to the gold labelled second antibody, was found. HNE was also present, however, in the granules of neutrophils in the same sections. Non-specific labelling associated with elastin was probably due to binding of IgG to the high numbers of hydrophobic and charged regions known to be present in this molecule, and it is concluded that our findings do not support the existence of high concentrations of elastase in association with elastin in emphysematous lung tissue.

Apocrine carcinoma of the breast containing foam cells. An electron microscopic and immunohistological study.

The detailed light and electron microscopic and immunohistological features of an invasive apocrine carcinoma of the breast developing in a 78-year-old woman are presented. The stroma of the tumour contained non-neoplastic lipid-filled (foam) cells. To our knowledge, these cells have not been described before in invasive breast carcinoma. Their electron microscopic and immunohistological features confirm their histiocytic nature.

Fuchs' heterochromic cyclitis: an electron microscopy study.

Electron microscopy and computerised image analysis of iris biopsies in five cases of Fuchs' heterochromic cyclitis showed that depigmentation was due to significant reduction in deep stromal melanocyte numbers and a decrease in melanosomal size, in the presence of more mast cells and an infiltrate of plasma cells and lymphocytes. Anterior border cells appeared sparse and their melanosomes showed similar differences when compared to five normally pigmented controls. Pigment epithelium melanosomes did not alter in size.

Alveolar variant of invasive lobular carcinoma of the breast: an electron microscopic study.

Four cases of alveolar variant of invasive lobular carcinoma of the breast were examined by electron microscopy, and their appearance compared with those of in situ and classical invasive lobular carcinoma. The individual tumor cells in the alveolar variant were basically similar to those described in the other two lobular tumors. The neoplastic alveoli consisted mostly of light cells, although a few dark cells were sometimes seen at the periphery. The nuclei were large, rounded and rich in euchromatin. The cytoplasm contained a variable amount of mitochondria and endoplasmic reticulum, and a few cells had intracytoplasmic filaments. Numerous tumor cells with membrane-bound electron-dense granules were occasionally seen. A few cells also had intracytoplasmic lumina. Tumor cells were usually seen in close contact with each other. Interdigitating processes and desmosomes were present. In general the tumor cells were not surrounded by basal lamina, but most alveoli were surrounded by elongated fibroblasts or myofibroblasts. These findings confirm both the lobular and the invasive nature of this distinct variant of breast carcinoma.

The ribosome-lamellar complex; is it a normal structure?

Ribosome-lamellar complexes were seen in mast cells in the iris of a patient with Usher's syndrome (retinitis pigmentosa associated with deafness) and in the neoplastic cells of an alveolar soft part sarcoma of the thigh. These 'organelles', originally described and associated with haematopoietic malignancy, where they have been described as the hallmark, are being increasingly often described in neoplastic and nonneoplastic cells. We believe that their usefulness in diagnosis should be questioned and the concept of their association with malignancy abandoned.

Type IV melanosomes of the human albino iris.

Electron microscopy of an iris biopsy specimen from a clinically tyrosinase-negative human albino demonstrated type IV mature melanosomes. Possible mechanisms for the formation in this condition of these organelles, which have not previously been described at this site, are discussed.

Secondary amyloidosis of the gastrointestinal tract: an electron microscopic study.

Biopsy specimens of the gastric antrum, duodenum, and rectum from three patients with secondary amyloidosis were examined by electron microscopy in an attempt to determine the ultrastructural distribution of amyloid filaments and to identify any secondary changes in the covering mucosal epithelial cells. The characteristic amyloid filaments were seen in the walls of submucosal arterioles and mucosal capillaries deposited within the basal lamina surrounding the endothelial cells. Filaments were also sometimes seen within the muscularis mucosa. the overlying gastric and rectal epithelial cells appeared normal, but numerous curved bacilli were seen in close contact with the microvilli of the surface epithelial gastric cells. Duodenal columnar absorptive cells were vacuolated and contained prominent lysosomes. These changes are probably degenerative and may explain, at least in part, the development of malabsorption in some patients with intestinal amyloidosis.

Squamous cell carcinoma of the breast.

We saw two cases of pure squamous cell carcinoma of the breast, one of which is associated with dermatomyositis. Electron microscopy of appropriately fixed tissue obtained from one tumor confirmed the squamous nature of the polyhedral and spindle-shaped tumor cells. One tumor was assayed for estrogen and progesterone receptor proteins and was found to be lacking both. Test results for mucin and carcinoembryonic antigen (CEA) were negative in both tumors. In contrast, a similarly examined case of invasive ductal carcinoma with areas of squamous metaplasia had slightly elevated concentrations of estrogen and progesterone receptor proteins, and test results for mucin and CEA were positive.

Chronic duodenitis with gastric metaplasia: electron microscopic study including comparison with normal.

Duodenal biopsies from 11 patients with non-ulcer dyspepsia were examined by electron microscopy. Chronic duodenitis with gastric metaplasia was seen in samples from four patients, and areas of normal-looking duodenal mucosa were present in nine. The metaplastic cells were similar to those previously described in association with duodenal ulcers. They usually showed marked morphological differences from the normal duodenal absorptive cells. The microvilli were distorted and reduced in number, the glycocalyx was ill-defined, the cytoplasm filled with mucous globules and the intercellular spaces, in some areas, were widened and contained acute and chronic inflammatory cells.

The distribution and assessment of electron-microscopic abnormalities of human cilia.

The aim of this study was to overcome difficulties of assessing the true incidence of electromicroscopic abnormalities of microtubular structure of cilia by examining large numbers of cilia from each case. The effects of different fixatives on the appearances of cilia were also studied. Bronchial biopsies were examined from 35 subjects who were being investigated for various lung diseases and nasal biopsies from 12 subjects (7 with retinitis pigmentosa (R.P.), and 5 healthy controls). Numerous pieces of normal looking bronchial wall from a lobectomy specimen were used to examine the effect of six different fixatives. 2.9% of bronchial cilia (mean of 890 cilia examined) and 2.4% of nasal cilia (mean of 808 cilia examined) showed microtubular abnormalities. Examining large numbers of cilia established that increased microtubular abnormalities were associated with smoking, chronic pulmonary infection and carcinoma of the lung. There was a significant increase (p less than 0.001) in microtubular abnormalities in nasal cilia in R.P. The appearances of cilia varied considerably with different fixatives. The numbers of dynein arms seen and the ease of recognising radial spokes and microtubules was particularly effected by fixation. The true incidence of microtubular abnormalities can only be ascertained by examining large numbers of cilia.

The significance of ultrastructural abnormalities of human cilia.

The electronmicroscopic structure of cilia was studied from the inferior turbinate of the nose in 22 adults, and in 84 biopsies from the bronchial tree of 40 adults. The incidence of compound cilia and abnormal microtubular structures was assessed. There were significant variations in the incidence of abnormalities in different parts of the airways and even within different areas of the same electronmicroscopic section. The focal nature of differences in structure of cilia indicate that abnormalities found in a single biopsy do not necessarily reflect a generalized change in the bronchial tree. Thus, such a finding should not be used as evidence that the abnormalities of cilia are the cause of decrease in mucociliary clearance or that they play a role in the pathogenesis of bronchiectasis and sinusitis.