As you like it, Part 3: A critique and historical review of calcification as seen with the electron microscope.

As You Like It, Part 3, is a continuation of the lectures given by the author (Ultra Path VIII and Ultra Path IX). It is a critical historical review of topics of interest to electron microscopists, attempting to show what went wrong and perhaps also why. The topics chosen this time demonstrate the prominent role electron microscopy has played in elucidating the diverse ways in which calcification can occur. The classic concept of dystropic and metastatic calcification is now inadequate to explain all observed phenomena. The electron microscope shows that calcification occurs in many different intracellular and extracellular sites and that each has its own morphology and etiology. Thus, a new classification based on ultrastructural morphology is born, but few seem to be aware of it. The author examines the ubiquitous but not too well-known phenomenon of cell remodeling, which often, but not always, leads to calcification. Topics are presented under the following headings: (1) matrical lipidic debris, (2) spherical microparticles, (3) matrix vesicles, (4) intramitochondrial calcification, (5) intralysosomal calcification, (6) calcification of collagen, (7) calcification of elastic fibers, and (8) calcification of secretory products.

As You Like It, Part 2: A critique and historical review of the electron microscopy literature.

As You Like It, Part 2, is a continuation of the lecture given at UltraPath VIII in 1996. It is meant to be a critical historical review of some topics of interest to electron microscopists that will show what went wrong and perhaps also why. Topics are presented under the following headings : (1) Amianthoid Fibers and Giant Collagen Fibrils, (2) Ribosome-Lamella Complex, (3) Globular Filamentous Bodies, and (4) Siderosomes, Hemosiderin vs. Ferritin.

Melanosis thyroidi.

Despite many studies on melanosis thyroidi, there is no consensus concerning the nature of the pigment or its pathogenesis. Here the past literature on this subject is reviewed and results are reported on a case of melanosis thyroidi that provides fresh insight into the nature of the pigment and its genesis. Briefly, the conclusion is that while a few of the pigment granules are classic lipofuscin granules (i.e., single-membrane-bound structures containing electron-dense material in the form of particles, granules and masses, and electron-lucent lipid droplets), a majority of the pigment granules also contain colloid, which is easily identified by its particulate substructure similar to the colloid in the lumen of follicles. Thus, these pigment granules are, in fact, ambilysosomes, where degradation of both endogenous (organelles) and exogenous (colloid) material occurs. Several phagosomes containing colloid were also seen in the thyroid epithelial cells.

As you like it.

I have developed something of a reputation for criticizing freely and frequently at our meetings and in my writings. You say you like this and find it useful and entertaining. As you like it, you are welcome to more of it. My comments and criticisms are presented under the following headings: (1) criticize at your peril; (2) how it all started (unjustly accused!); (3) abbreviations (a source of perennial aggravation, confusion, and waste of time); (4) mysterious bodies in mesotheliomas; (5) call a crystal a "crystal," not a "crystalloid"; (6) electron microscopy-a study of osmium artifacts; (7) length-to-diameter ratio of microvilli (mission impossible); (8) lamellar bodies (a popular but debased term); (9) amyloid filaments, not fibers; (10) filaments and microtubules do not branch; (11) there is no such thing as pseudomelanosis; (12) botched histochemistry (just about every gastrointestinal tract pigment was misdiagnosed by histochemistry); (13) intranuclear Russell bodies, not "Dutcher bodies"; and (14) nuclear pores and virus-like particles (a new development in an old farce).

Globular smooth-tubule aggregates in thanatophoric dwarfs.

A presumably new structure that we have called "globular smooth-tubule aggregate" was found in the cytoplasm of chondrocytes of 4 thanatophoric dwarfs. To the best of our knowledge these sharply delineated, rounded, sieve-like bodies of distinctive morphology have not been reported to occur in any other site or situation. Hence these structures may be of some diagnostic value. Continuity between the rough endoplasmic reticulum and smooth tubules in the aggregates was detected. Therefore it is suggested that smooth tubules in these aggregates derive by growth and extension from the rough endoplasmic reticulum.

Giant desmosomes in tumors.

The lengths of desmosomal profiles were measured in sections of tumor tissue from cases of mesothelioma, adenocarcinoma, squamous cell carcinoma, thymoma, and meningioma. Giant desmosomes (length of profile 1 micron or greater than 1 micron) were found in all the above-mentioned tumors except adenocarcinomas. The largest desmosomal profile in adenocarcinoma was approximately 0.8 micron long; the largest in mesothelioma was approximately 2 microns long. Our observations suggest that one of the ways in which giant desmosomes arise is by growth and fusion of adjacent desmosomes. Giant desmosomes may at times help in distinguishing mesothelioma from adenocarcinoma, but this is a rather rare phenomenon. In this study giant desmosomes were found in only 2 out of 10 cases of mesothelioma.

Pigments of the gastrointestinal tract: a comparison of light microscopic and electron microscopic findings.

It is now apparent that light microscopy and histochemistry failed to identify correctly the nature and composition of pigments in various gastrointestinal tract melanoses. In most instances it was thought that the pigment was melanin or a melanin-like substance. Electron microscopy (EM) and electron-probe energy dispersive x-ray analysis have rectified these errors and have shown the following: in melanosis coli the pigment granules contain lipofuscin; in melanoses ilei the pigment granules may contain either silicates and titanium or hemosiderin; and in melanosis duodeni the pigment granules contain iron sulfide. In melanosis esophagi it is not clear what the pigment is; it could be melanin or lipofuscin.

Noncalcific cusp thickening in Ionescu-Shiley cardiac valvular bioprostheses.

This study was undertaken to examine the morphological basis for noncalcific cusp thickening in 20 standard-profile Ionescu-Shiley bovine pericardial cardiac valvular bioprostheses (16 aortic, four mitral) with primary valve failure due to cusp tears. The patients included 17 males and three females, with a mean age of 52.0 years; their valves had been implanted for a mean of 105.8 months. All cases had variable degrees of "plasma insudation" without correlation to identifiable patient parameters. This was accentuated in individual valves in the cusp with the most extensive tears. In addition, the three valves with the thickest cusps were grossly distorted by massive deposits of amyloid (identified as AL-amyloid in two index cases studied). Two other valves had incidental amyloid deposits, identifiable only by electron microscopy. Amyloid involvement of pericardial bioprostheses has not been previously reported. The literature pertaining to amyloid involvement and plasma insudation of bioprostheses is reviewed.

Melanosis (haemosiderosis) ilei.

We report here a case of melanosis ilei where grossly visible greyish black pigmentation of the ileal mucosa was discovered at autopsy. Light microscopy showed Prussian blue positive pigment granules in macrophages in the lamina propria forming the core of villi. Ultrastructural examination showed that the pigment granules had the morphology of siderosomes which are known to be the electron microscopic equivalent of the haemosiderin granules seen with the light microscope. We know of no previous report where pigmentation of the ileal mucosa was ascribed to the presence of haemosiderin.

Melanoses of the gastrointestinal tract.

Electronmicroscopy and electron probe energy dispersive X-ray analysis studies have substantially contributed to our understanding of the various gastrointestinal tract melanoses. The nature of the pigment granules which occur in the various melanoses is discussed; their pattern of distribution in melanosis coli, melanosis ilei, melanosis duodeni and melanosis oesophagi is summarized and current knowledge of the aetiology and pathogenesis of these conditions is reviewed. Brief mention is also made of other examples of lipofuscin pigmentation, and a case of haemosiderosis ilei is described.

A comparison of the ultrastructure of pigment granules in melanosis ilei and pulmonary lymph nodes.

Two cases of melanosis ilei were studied, in which grossly visible blackish pigmentation of the ileal mucosa was incidentally discovered at autopsy. Light microscopy showed that the pigment granules lay within macrophages in atrophic Peyer's patches. Ultrastructural studies showed that the pigment granules were heterolysosomes containing crystalline material, particles, granules and, occasionally, lipid droplets. The morphological similarity between these pigment granules and granules in pulmonary macrophages was established through ultrastructural studies of pulmonary lymph nodes obtained during routine autopsies. These data, plus results of past electron-probe X-ray analytic studies by us and others, leads us to conclude that the pigment granules in melanosis ilei contain exogenous material derived from inspired and ingested materials.