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The relevance of ultrastructural examination in the classification of primary lung tumours.

Biopsies from 50 primary lung tumours were classified according to the World Health Organisation's Histological Typing of Lung Tumours. They were also subjected to electron microscopic examination. Comparison of the diagnoses made by these separate methods showed that many poorly differentiated squamous cell carcinomas had been incorrectly classified. Agreement was good in the diagnosis of adenocarcinoma whilst ultrastructural examination of small anaplastic carcinomas disclosed a neuroendocrine tumour with a combination of squamous and glandular elements. Large cell anaplastic carcinoma proved to be a 'waste-basket' containing tumours which displayed ultrastructural characteristics of poorly differentiated squamous cell carcinoma, poorly differentiated adenocarcinoma or neuroendocrine carcinoma. Electron microscopy was also valuable in characterization of other pulmonary tumours whose identity could not be resolved at the light microscopic level. Ultrastructural examination may provide a better understanding of the histogenesis and derivation of lung tumours, as well as their behaviour and therapeutic response.

Adenocarcinoma↗

Ultrastructural immuno-gold localization of immune deposits in human renal biopsies.

Ultrastructural immunolocalization of immunoglobulins has the potential to supply new information about immune-mediated glomerulonephritides. Most previous studies have used immunoperoxidase pre-embedding techniques to identify the components of glomerular deposits. These techniques have not been satisfactory as they only allowed the identification of one antigen (immunoglobulin) in each portion of tissue under investigation and also caused obliteration of labelled structures by the dense reaction product. Several studies have used colloidal gold as a post-embedding label, but these have been unable to localize immunoglobulins or complement components in epoxy resin embedded tissue. The present study uses glutaraldehyde-fixed tissue which is embedded in a polar acrylic resin. This technique results in good ultrastructural detail while allowing maximum antigen retention and, when combined with colloidal gold labelling, it provides the optimal procedure for ultrastructural immune localization. A spectrum of immunologically induced renal diseases is examined using this technique, the results of which correlate well with immunofluorescence.

Complement System Proteins↗

Histomorphology and ultrastructure of spontaneous pulmonary neoplasms in strain A mice.

The microscopic and ultrastructural characteristics of spontaneous pulmonary neoplasms in strain A (strA) mice are described. Fifty-one spontaneous lung tumors were identified in 34 out of 57, 11-23-month-old male strA/Hen mice. Grossly, all tumors appeared as yellow-white, discrete nodules ranging in size from 1.0-10 mm. Tumor types were randomly distributed throughout the lung; however, the right lung lobes were most frequently involved. Histologically, tumors were classified as adenoma (34/51) or carcinoma (17/51) as defined by standard histopathologic criteria. Adenomas were usually less than 4 mm in diameter and had solid (16/34), papillary (10/34), or mixed (8/34) histologic growth patterns. Carcinomas were usually greater than 4 mm in diameter and had papillary (13/17) or mixed (4/17) histologic growth patterns. Ultrastructurally, benign tumors consisted of solid or papillary areas of neoplastic type II-like cells. Cells comprising malignant tumors had varying ultrastructural characteristics ranging from well-differentiated alveolar cell types to undifferentiated cells having intracytoplasmic osmiophilic dense bodies, vacuoles, or few specialized organelles commonly observed in mature nonneoplastic pulmonary epithelial cells.

Adenoma↗

Ultrastructural analysis of apocrine carcinoma of the human breast.

A case report with ultrastructural analysis of an apocrine carcinoma of the breast is presented. The key finding with electron microscopy is numerous large mitochondria with abundant incomplete cristae. The ultrastructure of this tumor is compared to the ultrastructure of apocrine cells in the skin, oncocytes, and apocrine metaplastic cells of the breast. The apocrine carcinoma cells have some of the features of typical metaplastic breast epithelium and some features of oncocytes. Their exact origin remains open to speculation.

Apocrine Glands↗

Ultrastructure of congenital cystic adenomatoid malformation of the lung.

Four cases of congenital cystic adenomatoid malformation of the lung are presented with ultrastructural analysis. In some of the cases the ultrastructure is similar to that described in normal fetal airways during the early embryonic phase of lung development. Varying degrees of differentiation are noted, confirming what has previously been observed ultrastructurally in this lesion. One new finding is the presence of tonofilaments in one of our cases, which may represent a metaplastic change. Although the exact nature of the insult is unknown, there may be a developmental defect affecting epithelial differentiation as well as the interaction between the developing pulmonary mesenchyme and distal respiratory units.

Cell Membrane↗

Ultrastructure of the liver in th cerebrohepatorenal syndrome of Zellweger.

Three infants with clinical and biochemical features of Zellweger's cerebrohepatorenal syndrome are presented, and the ultrastructural features of successive biopsy and autopsy liver specimens are described. No hepatocellular peroxisomes were found in these patients on routine electron microscopy or electron microscopic histochemistry. In a control group of liver biopsies from 9 patients with other pediatric liver diseases, peroxisomes were readily identifiable in each hepatocyte. Apart from the absence of peroxisomes, the hepatocytes had a remarkably "normal" aspect, even in the final stages of the disease. Mitochondrial abnormalities, which have been the subject of some controversy in this syndrome, were a highly variable and inconstant finding in our cases. We draw attention to another ultrastructural feature of the syndrome, namely the occurrence of large angulate lysosomes, containing conspicuous double lamellae, inside macrophages, which were especially abundant in later stages of the disease. These angulate lysosomes may be of additional value in the ultrastructural diagnosis of Zellweger's syndrome, especially when only poorly preserved liver tissue (e.g., paraffin-embedded or postmortem material) is available, and the absence of peroxisomes is difficult to assess. In these instances, the angulate lysosomes can still be identified with ease.

Brain Diseases↗

Embryonic ultrastructure as a guide in the diagnosis of tumors.

The purpose of this article has been to illustrate the applications and limitations of comparing the ultrastructural morphology of certain poorly differentiated neoplasms with normal human embryonic tissues. The examples used--embryonal rhabdomyosarcoma, Wilms' tumor, and fibrous mesothelioma, in comparison with embryonic mesoderm and its early derivatives--are but a few of the entities that can be investigated in this manner. Ewing's sarcoma was included in the report because of the long-standing and unsolved mystery concerning its histogenesis and because we believe it probably fits into the same category of poorly differentiated mesodermal neoplasms as the other lesions described. However, unlike the other more definite examples of primitive neoplasms manifesting focal markers of secondary mesenchymal differentiation, Ewing's sarcomas exhibit no ultrastructural evidence for myogeneous, nephrogenic, or mesothelial lines of maturation. Nor are there any morphologic indications of ectodermal or endodermal differentiation. The questions arise as to whether the category of Ewing's sarcoma has been perpetuated by so classifying all small-cell neoplasms having no recognizable line of differentiation, and whether this category may include cells of more than one type, that is, cells that are biologically determined to develop along several different pathways. This concept would be one explanation for the occurrence of Ewing's tumors in soft tissue as well as in bone, and we know that the cells contained in somites are ultrastructurally very similar to the least-differentiated cells making up the myotomes and sclerotomes. Apparently, questions such as these cannot be answered by morphologic studies alone. However, a number of other useful diagnostic and academic points of information can be gleaned.

Embryo, Mammalian↗

Ultrastructure of renal adenoma.

Renal adenomas, defined as minute cortical foci of proliferating epithelium, are frequently occurring lesions reported to be present in 15%-22% of all adult human kidneys. They can often be found in kidneys with renal cell carcinoma. Their light microscopic structure makes it improbable that they should represent intrarenal metastases. The concept does not include clear cell foci. Ultrastructure of these cortical foci in human kidneys is not well known. A series of 10 intrarenal adenomas in carcinoma-bearing kidneys has been studied using tissue fixed rapidly after nephrectomy by perfusion with 2% glutaraldehyde. The results confirm their tubular origin. Ultrastructural markers of different segments of the nephron were demonstrated. Several of these markers might be present in each single case. The interpretation is that their ultrastructural characteristics do not indicate an origin from a special segment of the nephron. They may reflect an abnormal gene expression associated with the neoplastic change of the cell clone. Some changes are similar to those seen in cells from renal cell carcinoma, although not as prominent as in malignant cells.

Adenoma↗

Malignant fibrous histiocytoma of soft parts: an ultrastructural quantitative study.

Thirty-two cases of soft tissue malignant fibrous histiocytoma (MFH), including 24 of common storiform-pleomorphic type, 7 of myxoid type, and 1 of inflammatory type, were analyzed in an ultrastructural quantitative study, the objective being to clarify the cellular composition and distribution of the tumor. Approximately 100 unselected cells in each tumor were classified into seven types as follows: undifferentiated (10%-62%, m: 29%), histiocytelike (8%-69%, m: 37%), fibroblastlike (0.9%-26%, m: 11%), myofibroblasts (0%-22%, m: 3%), intermediate between histiocytelike and fibroblastlike cells (1%-41%, m: 15%), multinucleated giant (0%-1%), and xanthomatous cells (0%-1%). The undifferentiated, histiocytelike, fibroblastlike, and intermediate cells constituted the principal types, invariably present, although in varying proportions in each tumor. No statistical difference in ultrastructural cellular composition was evident in different portions of the same tumor, and such was also the case between the two main subtypes of MFH, common and myxoid. Naphthyl thiol acetate (NTA) esterase was demonstrated in fibroblastlike cells, using the ultrastructural cytochemical technique, in both cases examined. The possibility that MFH may be of alternative undifferentiated mesenchymal cell origin has to be considered.

Adult↗

Ultrastructural features of neuroendocrine differentiated carcinomas of the breast.

The ultrastructural patterns of neuroendocrine (NE) differentiated breast carcinomas are analyzed and discussed. Reports in the literature describe wide variations in the size of observed dense-core membrane-bound granules and discrepancies in their interpretation. In the present study 24 cases of breast carcinoma with recognized morphologic, histochemical, and immunocytochemical features of NE tumors were investigated. Five different types of dense-core granules of neurosecretory (NS) type (confirmed by the ultrastructural localization of chromogranin A) and five different cell types were recognized. Some amphicrine cells were found to contain both mucin and NS granules. Another notable ultrastructural feature of breast NE carcinomas was the presence of clear vesicles of presynaptic type, which correlated with expression of synaptophysin.

Aged↗

Ependymoma: ultrastructural studies of two cases.

Several unusual ultrastructural findings in two ependymomas are reported. In case 1, a grade I ependymoma of the fourth ventricle, there were rosettes, perivascular pseudorosettes, and tumor cells having unusual intracytoplasmic vacuoles by light microscopy. Ultrastructurally, these vacuoles were frequently microrosettes as well as scattered, degenerated cytoplasmic processes of tumor cells. The lumina of some of the microrosettes were bordered by abnormally long and malformed zonulae adherentiae. In case 2, a recurrent grade III ependymoma of the third ventricle, there were rosettes and perivascular pseudorosettes as well as more cellular and anaplastic areas by light microscopy. Ultrastructurally, the cytoplasmic processes of tumor cells in perivascular pseudorosettes contained frequent dense-core vesicles and occasional parallel arrays of microtubules. These structures do not occur in normal mammalian ependymal cells but do occur in the ependymal tanycyte, a related cell that is plentiful in the walls of the third ventricle. Thus some of the tumor cells of this third ventricle ependymoma appear to have differentiated as tanycytes.

Aged↗

Signet ring cell carcinoma of the stomach: a morphometric, ultrastructural, and DNA cytometric study.

The present study was undertaken to determine whether or not signet ring cell (diffuse, isolated cell) gastric carcinomas display a specific profile at the ultrastructural, morphometric, and DNA cytometric levels. Thirty-two cases of gastric carcinoma and 8 cases of peptic ulcer (control group) were studied with electron microscopy, morphometry, flow cytometry, and image cytometry. Despite the ultrastructural cellular heterogeneity of signet ring cell carcinomas, the neoplastic cells display fairly constant morphometric features: The cellular and nuclear volumes are significantly smaller than those of the other types of gastric carcinomas and closely resemble those of normal foveolar cells. The relatively small size of signet ring cell carcinoma nuclei fits with the high percentage of the cases of this type of gastric carcinoma that are either diploid or nearly diploid. There is a relationship between the infiltrative pattern of growth of gastric carcinoma (regardless of histologic subtype and ultrastructural cell differentiation) and the small size of neoplastic cells and their nuclei.

Adenocarcinoma, Mucinous↗

Ovarian myxoma: ultrastructural and immunohistochemical findings.

The ultrastructural and immunohistochemical findings are reported in two ovarian myxomas, one of which was also associated with a sclerosing stromal tumor of the same ovary. Both neoplasms showed a myxoid, moderately cellular proliferation of spindle and stellate cells interspersed with areas of fibrosis and hemorrhage as well as delicate vascular spaces. Ultrastructurally, stellate neoplastic cells with irregular nuclei and occasional nucleoli were embedded in a mucinous and loose collagen matrix. Their cytoplasm showed abundant intracytoplasmic thin filaments that rarely condensed into poorly formed dense bodies. These thin filaments correlated with immunoreactivity for muscle-specific actin and vimentin. The neoplastic cells showed no immunoreactivity with antibodies to desmin, S-100 protein, cytokeratin AE1:AE3, factor VIII-related protein, or placental alkaline phosphatase. These ultrastructural and immunohistochemical findings are consistent with myofibroblastic differentiation. These ancillary studies exclude important, clinically more aggressive differential considerations such as myxoid rhabdomyosarcoma, myxoid liposarcoma, myxoid neural tumors, mucinous adenocarcinoma showing pseudomyxomatous change, and myxoid-appearing endodermal sinus (yolk sac) tumor.

Actin Cytoskeleton↗

Ultrastructural study of a pituitary adenoma (prolactinoma) within the clivus bone using immunoelectron microscopy.

In a case of a pituitary adenoma in the clivus bone in a 71-year-old man, ultrastructural investigation using conventional aldehyde-fixed, epoxy-embedded tissue revealed the tumor to be composed of cells with euchromatic nuclei, dense nucleoli, abundant rough endoplasmic reticulum, spherical secretory granules, and granule extrusion at the lateral cell surface, all of which suggest a prolactin-producing adenoma. Using a protein A-gold immunolabeling technique on snap-frozen tissue subsequently fixed in a mild fixative and embedded in a hydrophilic resin, the presence of prolactin immunoreactivity within secretory granules at the ultrastructural level was demonstrated. This case represented the first use of protein A-gold immunolabeling at the electron microscopic level for diagnostic purposes at our institution and exemplifies the value of this technique when the need for diagnostic immunoelectron microscopy is not anticipated. Because this tumor arose in an unusual location, ultrastructural study, including immunoelectron microscopy, not only confirmed the light microscopic diagnosis of pituitary adenoma, but further allowed subclassification of the tumor.

Aged↗

Renal parenchymal malakoplakia: ultrastructural findings in different stages of morphogenesis.

Light microscopic and ultrastructural findings in five cases of renal parenchymal malakoplakia detected in renal biopsy specimens (four cases) or observed at autopsy (one case) are reported. The spectrum of ultrastructural changes ranging from lamellar and microvesicular phagolysosomal inclusions arranged in a biphasic pattern to fully developed Michaelis-Gutmann bodies is described. In three of the biopsy cases the lesions appeared to represent early stages of malakoplakia lacking classic Michaelis-Gutmann bodies. Especially in this phase of disease, ultrastructural investigation can distinguish between this condition and other histiocytic interstitial renal processes. The findings show that focal cytoplasmic degeneration and autophagolysosomal processes observed in macrophages could precede the disturbance in the process of bacterial breakdown that is responsible for the peculiar granuloma-like inflammatory histiocytic reaction.

Adult↗

Ultrastructural pathology of Gerstmann-Sträussler-Scheinker disease.

We report a detailed ultrastructural study based on a large series of samples from a recent case of Gerstmann-Sträussler-Scheinker disease from the original Austrian family. Numerous PrP-immunopositive plaques dominated light microscopic neuropathology. Ultrastructurally, several types of plaques were observed: unicentric "kuru," multicentric, and neuritic. Dystrophic neurites accompanied amyloid plaques to differing degrees. Plaques were enveloped by astrocytic processes and invaded by microglial cells. A prominent astrocytic reaction accompanied abundant spongiform change. Unusual crystalloids were observed in mitochondria while another type of crystalloid was seen within lysosomes. We conclude that Gerstmann-Sträussler-Scheinker disease is distinct also at the ultrastructural level.

Amyloid↗

Abnormal melanosomes: ultrastructural markers of melanocytic atypia.

To identify possible ultrastructural markers of melanocytic atypia, a quantitative ultrastructural study was made of melanocytes found at the dermal-epidermal boundary of normal skin and in benign, premalignant, and malignant melanocytic lesions. There was a significant increase (p < 0.05) in the number of melanosomes per melanocyte in the premalignant and malignant lesions compared with the number observed in the benign lesions. There was a significantly higher number (p < 0.05) of abnormal melanosomes (with irregularities in the laminar matrix or with a granular or clumpy matrix) in the premalignant and malignant lesions, which suggests that the presence of a high percentage of abnormal melanosomes might act as a useful ultrastructural marker in the diagnosis of melanocytic atypia.

Adult↗

Spindle cell and pleomorphic lipoma: an ultrastructural study.

Spindle cell and pleomorphic lipoma are rare benign tumors of adipose tissue. Their histogenesis is poorly understood and pleomorphic lipoma has not previously been studied ultrastructurally. This study describes the morphology and ultrastructure of 6 cases of spindle cell and pleomorphic lipoma. Both spindle cell and pleomorphic lipomas showed similar ultrastructural features with an interrupted basal lamina, occasional non-membrane-bound lipid vacuoles and abundant rER. In all the cases mast cells were conspicuous and were intimately related to both spindle and pleomorphic cells. It is proposed that both the spindle and pleomorphic multinucleated cells that characterize these tumors are prelipoblastic mesenchymal cells. The possible significance of an interaction between these cells and mast cells is discussed.

Cell Nucleus↗