Elastofibroma: disturbed elastic fibrillogenesis by periosteal-derived cells? An immunoelectron microscopic and in situ hybridization study.

Monospecific antibodies to elastic tissue components have been used for immunoelectron microscopy of two examples of elastofibroma. The elastic-staining fibers typically seen in these lesions exhibited a variety of morphologies with differing ratios of the amorphous and microfibrillar components usually seen in elastic fibers. The amorphous elastic material in these fibers had variable affinity for ionic stains and exhibited several substructural morphologies. Despite this, each form reacted specifically with anti-elastin antibodies. Most of the elastic fibers were associated with relatively large numbers of 12-nm diameter microfibrils that were typical of those associated with normal elastic fibers, and were specifically reactive with monospecific antibodies to microfibril-associated glycoprotein. In situ hybridization studies with a cRNA probe for human elastin confirmed that active elastin biosynthesis was occurring patchily within the lesions. The appearances and staining characteristics of the elastic tissue elements, the morphology of the cells, and the structure of the collagen fibers in these lesions were shown to have many features in common with those of normal periosteum. It is proposed that elastofibromas arise from the periosteum as a result of chronic irritation and that the different elastic fiber morphologies represent disturbances of elastic fibrillogenesis by periosteal-derived cells.

Cryptococcal epididymo-orchitis complicating steroid therapy for relapsing polychondritis.

Disseminated cryptococcosis is a known complication of steroid therapy. Infection within the genito-urinary tract is usually assumed to be part of generalized cryptococcosis complicating a primary pulmonary focus. A case of isolated testicular cryptococcal orchitis complicating steroid therapy for relapsing polychondritis is presented. To the authors' knowledge isolated cryptococcal orchitis has not been previously described.

IgA nephropathy--accumulated experience and current concepts.

Primary IgA nephropathy is the most common form of glomerulonephritis in Australia. The condition presents in a variety of ways, but commonly with synpharyngitic hematuria, most often in young men in the third and fourth decades. The course of the disease is indolent but there is progression to renal failure in up to one quarter of cases. Renal biopsy morphology is variable but the essential immunofluorescence finding is diffuse mesangial IgA staining of greater intensity but often in association with other immunoglobulins. C3 is usually also present. Mesangial cellularity is increased in some two-thirds of cases, one third being of a minor focal or variable extent and one-third diffuse. Focal segmental lesions, hyaline nodules and vascular changes are frequent. Crescents are also often present. The etiology of the disease is uncertain but has been linked with HLA antigens, elevated serum IgA levels, IgA polymers, immune complexes and impaired T cell function. Secondary forms of mesangial IgA deposition occur with mucosal defects, hyperglobulinemia or impaired hepatobiliary clearance, and these may offer some insight into the immunopathogenesis of the primary disease.

The syndrome of IgA nephropathy.

A review is presented of the current knowledge concerning the syndrome of IgA nephropathy. Primary and secondary forms can now be delineated and this division has improved understanding of immunopathogenetic mechanisms giving rise to glomerular mesangial IgA deposits. Attention is paid to disorders of antigen exclusion at mucosal surfaces, defective reticulo-endothelial sequestration, and altered immunoglobulin A production and regulation. Particular reference is made to these mechanisms with respect to primary IgA nephropathy, Henoch-Schoenlein purpura and mesangial IgA nephritis associated with alcoholic cirrhosis.

The immunochemical characterization of mesangial IgA deposits.

Mesangial deposits of IgA are found in IgA nephropathy, Schönlein-Henoch purpura (SHP) and in some patients with alcoholic cirrhosis and systemic lupus erythematosus (SLE). In this study the authors characterized the mesangial IgA deposits in patients with the above diseases using antiserums or monoclonal antibodies to A1, A2, J-chain and secretory component (SC), and examined SC binding in vitro. SC was not present, J-chain was ubiquitous, and A2 was found (with the use of monoclonal antibodies) rarely but with equal frequency in all groups. The SC binding capacity of the deposits differed between the groups and was found in 13 of 16 patients with alcoholic liver disease, 3 of 4 with SLE, 1 of 10 with primary IgA nephropathy, and none of 6 with SHP.

Mesangial IgA nephritis.

Current data suggest that mesangial IgA nephritis is mediated by the mesangial deposition of soluble antigen-IgA class antibody complexes from the circulation. It is likely that common infectious gut flora and dietary antigens contribute to the immune complex load. Defects in antigen exclusion at the mucosa, in the control of IgA production, and in immune complex clearance are postulated to account for each of the recognized clinical syndromes. As yet no effective treatment is available, and a detailed analysis of the mediation pathways will be required before prevention or therapy can be attempted.

Neoplasia in analgesic nephropathy. A urothelial field change.

The association between analgesic nephropathy and urothelial cancer, usually in the renal pelvis, is well established. We report two such patients in whom careful morphologic study of nephrectomy specimens demonstrated severe and extensive urothelial dysplasia, with focal carcinoma in situ and grossly invisible invasive tumors. In one of these patients, no gross lesion was apparent in the urothelium. These findings support the development of invasive carcinoma through a phase of carcinoma in situ caused by the action of carcinogenic analgesic metabolites in the urine. Further, they indicate the need for caution in the assessment of urinary cytologic atypia and for care in the examination of excised urothelium in those patients.

Unsuspected analgesic nephropathy in transitional cell carcinoma of the upper tract: a morphological study.

Analgesic nephropathy is known to have a high incidence in Australia where, following the experience in Scandinavia, reports have been published for some time recording the association between analgesic nephropathy and urothelial malignancies. The morbid anatomical features of analgesic nephropathy are now sufficiently well accepted to allow a retrospective study of unselected nephrectomies for transitional cell carcinoma of the renal pelvis and ureter, in order to assess the incidence of analgesic-type changes in this well defined group of malignancies. The records of a large general histopathology department between 1972-1978 were searched and 24 consecutive transitional cell carcinomas in these sites treated by nephrectomy were selected for study. Of these, 21 were suitable for assessment and on review were shown to comprise II cases with papillary changes acceptable as analgesic in type and five which were suggestive of early analgesic change. Of these 16, seven were female, only two were known analgesic abusers and five were recorded as consuming analgesics on a regular basis. These findings suggest that analgesics may play a significant role in the pathogenesis of urothelial malignancy in the general population.

The hyaline cell: a distinctive feature of "mixed" salivary tumours.

We have identified and described a distinctive type of cell which is characteristic of the "mixed" salivary tumour. This "hyaline cell" or plasmacytoid cell is particularly common and conspicuous in "mixed" tumours of the palate and other sites in the mouth. It occurs also in tumours of the major glands, but with much lesser frequency. The hyaline cell is found in "mixed" salivary-type tumours in other sites, e.g. the skin. It is not present in the other types of salivary tumour, notably adenoid cystic carcinoma, adenolymphoma, mucoepidermoid and acinic tumour. Ultrastructural study suggests that the hyaline cell is an indicator of myoepithelial differentiation. Current concepts of the acceptable pathways of myoepithelial differentiation in "mixed" tumours are discussed briefly. The specificity of the hyaline cell will probably prove valuable in separating "mixed" tumours from monomorphic adenomas, thus retaining the identity of the latter. The hyaline cell is almost as distinctive a feature of "mixed" tumours as is myxochondroid tissue and its specificity is of practical value in the diagnosis and classification of salivary tumours.