Ultrastructure of acute myeloid leukemia arising in multiple myeloma.

Bone marrow from a case of multiple myeloma in which acute myeloid leukemia supervened four years after diagnosis was examined with the electron microscope. Two distinct populations of neoplastic cells, one plasmacytoid and the other myeloid, were identified in the marrow. It is concluded that the acute leukemia that developed in this patient was a distinctly new neoplasm arising from the myeloid series of cells. Since in nearly all previously reported cases, and in our patient, alkylating agents had been administered, it is thought that this may have been a factor in the development of acute myeloid leukemia.

Foreign materials found in the cardiovascular system after instrumentation or surgery (Including a guide to their light microscopic identification).

Foreign materials are often seen by light microscopy in surgical or autopsy specimens sent from the cardiovascular clinical services. This paper describes the range of materials that may be recovered in such specimens and provides a pictorial guide to aid in their identification. The spectrum of medical and nonmedical foreign materials that may be encountered in the cardiovascular system is discussed.

Aurosomes produced by sodium chloroaurate.

Aurosomes were produced in the rabbit synovial membrane by injecting sodium chloroaurate. They contained electron-dense, filamentous, rod-like and lamellar profiles studded with particles and granules. These aurosomes are morphologically indistinguishable from aurosomes produced by sulphur-containing soluble gold salts such as sodium aurothiomalate and aurothioglucose. It is therefore concluded that the sulphur-containing portion of these molecules is not responsible for the characteristic morphology of the aurosome as claimed by others. However, electron-probe x-ray analysis of aurosomes produced by sodium chloroaurate showed the presence of gold, phosphorus and sulphur. It is concluded that the sulphur and phosphorus must have been derived from the biological milieu, since it could not have been derived from the injected compound.

Benign spindle cell tumour of breast--a variant of spindled cell lipoma or fibroma of breast?

A case of the so-called "benign spindle cell tumour of breast" is presented. Ultrastructurally, it is composed of fibroblastic cells cut in various planes. We believe that it is basically a fibroma. Its relationship to spindle cell lipoma is discussed.

Uraniosomes produced in the synovial membrane by uranyl acetate.

Uranyl acetate was injected into the rabbit knee joint. This produced single-membrane-bound presumably lysosmal bodies (called 'uraniosomes') containing electron-dense crystals in Type A and Type B synovial intimal cells, subsynovial macrophages and lipocytes. Uranium deposits were also seen in the extracellular matrix. All uraniosomes and extracellular deposits analysed by electron-probe X-ray analysis were found to contain uranium, potassium and phosphorus. Traces of calcium and sulphur were also found in some of the uraniosomes and extracellular uranium deposits.

Chloramphenicol-induced mitochondrial and ultrastructural changes in hemopoietic cells.

Bone marrow from a patient with bilateral staphylococcal bronchopneumonia who was treated with large doses of chloramphenicol was examined with the electron microscope. Our study supports the currently accepted concept that this drug depresses protein synthesis in mitochondria as it does in bacteria, since numerous alterations of mitochondrial morphology were encountered. These include (1) swollen mitochondria; (2) mitochondria with ruptured envelope; (3) mitochondria with longitudinally oriented cristae; (4) "ring" mitochondria; and (5) mitochondria with intramatrical iron deposits. The electron microscopical study discloses that the well documented vacuoles seen in marrow cells on light microscopy after treatment with this drug represent lipid droplets.

Nuclear fibrous lamina in the rheumatoid synovium.

Biopsy specimens of synovial membrane were obtained from patients with rheumatoid arthritis and from patients with nonrheumatoid conditions. Comparison of the mean thickness of the lamina in the rheumatoid and nonrheumatoid groups showed a statistically significant thickening of the lamina in the rheumatoid group (rho less than .01). There was no statistically significant difference in the thickness of the lamina before and after chrysotherapy.

Experimental methods of repairing injured menisci.

A longitudinal incision resembling a bucket-handle tear was made in the menisci of 8 rabbits, 6 dogs, 11 pigs and 12 sheep. In some of the animals of each species the cut was repaired by suturing, and in others it was not. Gross inspection, as well as examination by light and electron microscopy, showed that no healing had occurred after six months in the sutured or the unsutured wounds and that the meniscus was incapable of significant intrinsic repair. In a second experiment longitudinal, transverse and T-shaped cuts were made in the menisci of 12 sheep, and a flap of synovium was sutured into the wound. Three months later there was clear evidence of healing by the formation of cartilaginous tissue. Examination by light and electron microscopy showed that the newly formed repair tissue, possibly derived by metaplasia from the synovium, had a morphology intermediate between hyaline cartilage and fibrocartilage. Synovial implantation may therefore be considered as an alternative to meniscectomy in the management of the torn meniscus.

Electron probe X-ray analysis of an intraocular foreign body.

We describe a simple and rapid method of electron probe x-ray analysis on a foreign body removed from the eye. We demonstrated the presence of copper in an intraocular foreign body which has originated from a blank 0.22 calibre cartridge. Sodium, potassium, calcium, phosphorus, sulpher and chlorine were also detected. It seems likely that these elements were derived from the biological milieu in which the intraocular foreign body had rested for some 2 years and 9 months.

A comparison of the atomic composition of siderosomes (haemosiderin) in cryosections of unfixed frozen tissues and Epon-embedded tissues.

Siderosomes (i.e. single membrane-bound lysosomal bodies containing haemosiderin) were produced in the liver and muscle of rats by injections of iron dextran. Electron-probe X-ray analysis was executed on siderosomes in cryosections of quick-frozen fresh unfixed tissues (liver and muscle) and sections of Epon-embedded tissues. There were no statistically significant differences between the ratios of iron:phosphorus and iron:sulphur in these two types of preparations. Hence it is concluded that there is no significant loss or gain of phosphorus or sulphur during preparation of tissues for Epon embedding. The results confirm past belief that so little phosphorus or sulphur is present in siderosomes that haemosiderin is best regarded as ferric hydroxide oxide. A new finding in the present study was the demonstration of small amounts of potassium in siderosomes in cryosections. It seems that potassium is lost (leaches out) from siderosomes during preparation of tissues for Epon-embedding.

Anchoring fibrils in a spindle cell squamous carcinoma.

To the best of our knowledge anchoring fibrils in tumours have been reported to occur only in cutaneous cylindromas and squamous cell carcinomas of oral mucosa and larynx. In this paper we describe a difficult-to-diagnose malignant spindle cell tumour where the striking feature was the presence of large numbers of anchoring plaques and anchoring fibrils in the tumour matrix. On the basis of light microscopic and immunohistochemical studies several diagnoses were preferred, such as malignant fibrous histiocytoma, neurofibrosarcoma, malignant schwannoma, desmoplastic melanoma and spindle cell squamous carcinoma (more fully referred to as 'spindle cell variant of squamous cell carcinoma'). The presence of anchoring fibrils in this tumour strongly supports the diagnosis of spindle cell squamous carcinoma. Our knowledge about the occurrence of anchoring fibrils in tumours is scant, perhaps because they are likely to be missed unless they are present in large numbers, or perhaps because they are mistaken for native collagen fibrils. It seems to us that a systematic search for anchoring fibrils in tumours is warranted, for knowledge about their occurrence or absence in various types of tumours may add yet another diagnostic marker in the armamentarium of the diagnostic electron microscopist and it may also assist in resolving the histogenesis of some controversial neoplasms.

Diagnostic value of microvillus-matrix associations in tumors.

Until now microvillus-matrix associations have been reported to occur only in mesotheliomas and hence this phenomenon is thought to be of value in distinguishing mesothelioma from pulmonary adenocarcinoma. We report here the occurrence of microvillus-matrix associations in two pulmonary adenocarcinomas which reduces the value of this phenomenon in the differential diagnosis of these tumors.

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.

The morphology and atomic composition of aurosomes produced by sodium aurothiomalate in human monocytes.

Aurosomes were found in monocytes (from the peripheral blood of man) incubated with sodium aurothiomalate. In electron micrographs the aurosome presents as a single-membrane-bound lysosomal body with an electron-lucent or medium density matrix in which lie electron-dense filamentous (straight or curled), rod-like and lamellar profiles studded with particles and granules. Similar deposits did not develop in monocytes incubated with sodium thiomalate but myelinoid membranes and rod-like structures presumably derived from them were seen in the lysosomes of these cells. The aurosomes (and their characteristic electron-dense contents) produced in the monocytes in vitro were morphologically indistinguishable from those known to occur in various tissues of man and experimental animals treated with soluble goldsalts. The atomic composition of the aurosomes produced in vitro appears to be similar to that produced in vivo for in both instances Au, P and S can be demonstrated in the aurosome. It is concluded that the aurosomes produced in our experimental model is an accurate copy of that found in in vivo situations.

The technique of electron probe x-ray analysis and the atomic composition of aurosomes.

Electron probe x-ray analysis is an exciting new method of elemental analysis at the ultrastructural level. This is a relatively non-destructive form of analysis by which elements from Na onwards (i.e. above Z number 10) can be simultaneously detected and displayed as a spectrum. The best spatial resolution that can be achieved is of the order of 20 nm. The sensitivity of detection varies with the elements but about 10-18 g of an element can be detected. With the available computer programs elemental ratios are readily determined without the need of standards. The special appeal of this technique stems from the fact that it is the only way of analyzing minute inclusions in situ within the cell and so correlate morphology with atomic composition. With this method, gold has been demonstrated in aurosomes produced in various sites after the administration of soluble gold salts to experimental animals and man. A more detailed analysis of aurosomes found in the synovial membrane 3 days and 18 months after injection of gold sodium thiomalate into the rabbit knee joint revealed that the aurosome contains gold, phosphorus, and sulphur, and that the atomic ratios of these elements do not alter over the above mentioned time interval.

The aurosome.

Aurosomes are lysosomal bodies containing gold. Colloidal gold produces aurosomes containing spherical electron-dense granules. Soluble gold salts produce aurosomes containing lamellar, filamentous and rod-like profiles studded with particles and granules. This morphological pattern is quite distinctive, and is not affected or altered by which particular soluble gold salt is administered, by which route it is administered or in which species or cell type the aurosome occurs. In the skin of patients treated with soluble gold salts the characteristics electron-dense formations indicating the presence of gold are often found in compound melanosomes and other lysosomes in the dermal macrophages; while in the synovial membrane these characteristic electron-dense deposits are seen in the numerous lysosomes that develop in the rheumatoid synovial membrane. Thus it would appear that while aurosomes may vary somewhat in morphology, the electron dense contents indicating the presence of gold have a fairly constant morphology.