Biomedical subjects
F N Ghadially
Publications and source records attributed to F N Ghadially.
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.
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.
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.
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.
Osteosarcomatous changes in malignant melanoma.
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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.
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.
Is synovial sarcoma a carcinosarcoma of connective tissue?
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Intracisternal tubules in a case of chronic lymphocytic leukaemia.
In a case of chronic lymphocytic leukaemia we found that a few (less than 5%) of the circulating leukaemic lymphocytes contained inclusions of a type which do not appear to have been reported in the literature. The inclusions presented as solitary tubules or aggregates of parallel tubules lying within dilated cisternae of the rough endoplasmic reticulum and the perinuclear cistern. Some of the tubules were bounded by a single wall, others by a double wall. We also found a tubule bounded by three walls and another where a segment of the tubular profile was triple-walled and the remainder double-walled. We are inclined to think that the walls of these tubules are composed of membranes. The aetiogenic agent or agents responsible for the production of intracisternal tubules and their mode of formation are obscure.
A serial section study of tubular confronting cisternae (so-called 'test-tube and ring-shaped forms') in AIDS.
A serial section study was executed on a lymph node from a case of AIDS (acquired immune deficiency syndrome) to determine the true three-dimensional morphology and mode of genesis of tubular confronting cisternae which are found in the lymphocytes in this condition. Serial sections from over a hundred such structures show that these are tubular structures and that the 'test-tube and ring-shaped' forms described in the literature are no more than profiles one expects to see when a tubular structure is sectioned. The view at times expressed in the literature that these structures are truly test-tube-shaped (i.e. one end closed) appears to be erroneous, for our serial section study did not reveal a single instance where one end was closed; all were tubular structures with both ends open. We found that tubular confronting cisternae develop by a process of twisting and spiralling of ribbon-shaped confronting cisternae, and that at one stage of development there is a spiralling groove on the wall of this structure. Microtubuloreticular structures were seen in several lymphoid cells, sometimes they were found in cells containing tubular confronting cisternae. At times microtubules (similar to those seen in microtubuloreticular structures) were seen lying within and/or outside the profiles of dense lamina of tubular confronting cisternae.
Confronting cisternae complexes in Purkinje cells of a dog.
During the course of our studies on the cerebellum of a dog we found large eosinophilic inclusions in Purkinje cells. Ultrastructural studies revealed that these inclusion bodies are composed of aggregates of stacks of confronting cisternae or modified confronting cisternae. The nature and significance of these unusual inclusions is obscure.
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.
An ultrastructural study of age-associated changes in the rabbit synovial membrane.
The synovial membranes of 5 young rabbits about 6 weeks old and 5 older rabbits about 3-4 years old were studied with the light and electron microscopes, with a view to discovering any age-associated changes that might occur. Several age-associated changes were noted. These included: (1) a reduction in the overall population of synovial intimal cells; (2) a statistically significant reduction in type B cells and a relative increase in type A cells; (3) the emergence of atrophic cells poorly endowed with organelles; (4) decreased vascularity; and (5) fibrosis.
A comparative ultrastructural study of cutaneous blue naevi of humans and hamsters.
A comparative study of 12 human blue naevi and 15 carcinogen-induced hamster blue naevi showed no significant ultrastructural difference between these two groups of tumours. Both groups of tumours showed melanotic and hypomelanotic variants, and both were composed almost entirely of cells acceptable as melanocytes and melanophages. However, a few cells in some human and hamster tumours were partially or completely surrounded by a slender or quite thick external lamina. This may indicate a tendency towards a schwannocytic type of differentiation, but no other feature of schwannocytic differentiation such as the formation of mesaxons or pseudomesaxons was detected. Several cutaneous nerves were embedded in some of these tumours but they were clearly uninvolved in the neoplastic process and there was no evidence whatsoever that the tumours had developed from neural elements. We conclude that both human and hamster blue naevi are essentially melanocytomas which develop from dermal melanocytes which failed to reach the epidermis during development. We regard the occasional occurrence of an external lamina as an aberration of the neoplastic state which reflects the close kinship of melanocytes and Schwann cells i.e. their common origin from the neural crest.
Ultrastructure of an intraocular lacrimal gland choristoma.
An intraocular lacrimal gland choristoma which was at first mistaken for a medulloepithelioma (diktyoma) was studied with the electron microscope. The tumour did not contain cells with neuronal and glial differentiation as expected in a medulloepithelioma but it did contain acini, ducts and dilated ducts or cysts. The tumour, in fact, bore much resemblance to the lacrimal gland, in that it contained electron-dense serous granules, and at times, a myoepithelial cell was detected at the base of an acinus. The ductal and cystic elements were lined by a single layer of cells or by stratified or pseudostratified epithelium. An interesting, unexpected feature was the occurrence of a myoid band (composed of thin filaments with focal densities along their course) under the cell membrane of the epithelial cells adjacent to the lumen of the ducts and cysts.
Oncocytic carcinoid of the lung.
A case of oncocytic carcinoid of the lung was studied with the electron microscope. This rare tumour is composed of cells acceptable as neuroendocrine cells, oncocytes and cells of an intermediate morphology. Our studies lead us to believe that this tumour develops by oncocytic transformation of neuroendocrine cells in a carcinoid. Two new findings reported in this study are: 1) the occurrence of filamentous inclusions in mitochondria; and 2) calcified spherules which appear to develop in material secreted by tumour cells.