Mucinous anal gland carcinoma with perianal Pagetoid spread.

We report a case of well differentiated perianal mucinous carcinoma with associated dysplasia of the adjacent anal gland epithelium. Anal gland dysplasia is only rarely demonstrable histologically in cases of adenocarcinoma of suspected anal gland origin. The tumor was not associated with chronic perianal abscess or fistula formation, which had been regarded as important in the pathogenesis of perianal mucinous carcinoma. There was associated, clinically unsuspected Pegetoid intra-epidermal spread of adenocarcinoma in the perianal skin.

Abnormal integrin receptor expression in two cases of familial nephronophthisis.

Familial nephronophthisis is one of the inherited human cystic kidney diseases and is characterized by progressive renal failure. We have investigated abnormalities of cell-matrix interactions using immunocytochemistry and electron microscopy in three renal biopsies from two patients with familial nephronophthisis and compared our findings to those seen in thirty other renal biopsies. We found expression of the alpha 5 integrin fibronectin receptor in all three samples of nephronophthisis but in no other renal diseases. There was also enhanced expression of the alpha 2 integrin in nephronophthisis but this appeared to be a common response to tubular injury. Electron microscopy showed thickening of the tubular basement membrane and a loss of organization of the basal pole of tubular epithelium. We conclude that altered cell-substratum adhesion contributes to the pathogenesis of nephronophthisis.

Female adnexal tumour of probable Wolffian origin: a clinicopathological and immunohistochemical study of three cases.

The clinical and pathological features of three adnexal tumours of probable Wolffian origin are reported. One case was an incidental finding in a patient who died from ovarian carcinoma; in the other two cases the patients presented with lower abdominal pain. The three tumours were well-circumscribed, solid masses arising in the leaves of the broad ligament and histological examination showed bland epithelial cells forming tubular, solid and microcystic patterns. The immunohistochemical profile of the tumours was similar to that of Wolffian duct remnants. They co-expressed cytokeratin and vimentin and lacked epithelial membrane antigen (EMA) reactivity, in contrast to tumours of Müllerian origin which usually express EMA. The differential diagnosis of female adnexal tumours is discussed.

Fibrosarcoma arising in an ovarian mucinous tumor: a case report.

A case of an ovarian mucinous tumor with a mural nodule is reported. The mucinous tumor was solid and cystic and contained benign, borderline and malignant elements. Within the solid area a nodule representing fibrosarcoma was identified. Mucocoele of the appendix was the other finding in this case. To the best of our knowledge this is the first description of fibrosarcoma arising in an ovarian cystadenocarcinoma.

The specificity of integrin-ligand interactions in cultured human renal epithelium.

Members of the beta 1 integrin family are present at the basolateral membrane of human renal tubular epithelium in vivo and at the ventral surfaces of cultured renal epithelial cells, at the sites appropriate for cell substratum adhesion. In this study we have proven that these molecules are indeed functional in mediating cell substratum attachment in normal human renal epithelium by using monoclonal antibodies to integrin alpha subunits to block initial cell attachment. The importance of arginine-glycine-aspartic acid (RGD) recognition by cell surface receptors in various extracellular ligands was also examined using synthetic peptides. RGDS peptide strongly inhibited attachment to plain plastic or fibronectin-coated substrata but had no effect on cell adhesion to laminin-coated coverslips.

Metabolic requirements for phorbol ester-induced cytoskeletal changes in renal epithelium.

Alteration of the cytoskeleton and cell-substratum adhesion are important in the progression of renal carcinoma. We have previously shown that treatment of normal human renal epithelium with phorbol esters mimics the changes seen in renal carcinoma cells. In this study we have demonstrated that the phorbol ester-induced cytoskeletal reorganization is inhibited in the presence of deoxyglucose but not by cycloheximide. We have also shown that treatment of cells with cytochalasin B results in the formation of immature stress fibres restricted to the cell-substratum contact regions. These results suggest that the actin filaments elongate from the focal contacts and that structural rearrangement caused by phorbol esters is an energy-dependent phenomenon but is independent of de novo protein synthesis.

Polycystic kidney disease in the CBA/N immunodeficient mouse.

We describe a polycystic lesion of the kidney in the CBA/N mouse with an X-linked recessive immunodeficient syndrome. There is progressive cystic dilatation affecting all parts of the nephron. The cyst lining is composed of a single layered epithelium with focal nuclear crowding and the formation of micropapillary structures. The cystic epithelial cells show subnuclear vacuolation. Focal basement membrane thickening is also a feature. There is no significant inflammatory infiltrate present within these kidneys. Electron microscopic examination reveals that the subnuclear vacuolation is due to loss of the membrane infoldings at the basal pole of the epithelial cell with fluid accumulation within the extracellular space. The basement membrane thickening is due to expansion of the lamina densa. These changes are not present at birth but develop progressively with age. The finding of a polycystic kidney lesion in these mice offers an opportunity to investigate the relationship between the immune system and renal cyst formation.

Differential expression of integrin alpha chains by renal epithelial cells.

We have investigated the expression of integrin chains by human renal epithelial cells during in vivo renal differentiation and in vitro cell culture on different extracellular matrices. Using the immunoperoxidase technique to visualize the binding of monoclonal antibodies to different integrin chains in fetal and adult kidneys, we found a change during development from alpha 1 beta 1, alpha 3 beta 1, and alpha 4 beta 1-positive blastemal cells to alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 1-positive epithelial cells. The pattern of integrin expression correlates with the presence in the extracellular matrix of the appropriate ligands. In in vitro cell culture experiments, renal epithelium expressed alpha 3 and alpha 5 integrins on all extracellular matrices. Integrins alpha 2 and alpha 6 were found only in cells grown on a laminin-containing substratum. Fibronectin and alpha 5 integrin co-localized on the ventral surface of cells grown on a laminin substratum and at the periphery of cells on glass coverslips. These results suggest that there is a close relationship between integrin alpha chain usage and the presence of appropriate ligands in the extracellular matrix.

Minimal deviation endometrioid adenocarcinoma of cervix: a clinicopathological and immunohistochemical study of two cases.

We describe the clinicopathological features of two cases of minimal deviation endometrioid adenocarcinoma of cervix. This is a rare tumour whose predominant pattern is one of bland endometrial-type glands infiltrating the cervical wall without a stromal response. Thus, it may be confused with benign conditions such as cervical endometriosis. The two cases demonstrate that this tumour may behave aggressively despite its bland appearances. An immunohistochemical study was performed and showed only focal reactivity of neoplastic glands for carcinoembryonic antigen, which would limit its diagnostic use in small biopsy specimens.

A tumour promoter induces alterations in vinculin and actin distribution in human renal epithelium.

Loss of cell-substratum adhesion is an important factor during tumour progression. We have previously described reduced focal contact components and poorly organized cytoskeletal actin in renal cell carcinomas. In this study, we have used the potent tumour promoter TPA on cultured human renal epithelium to mimic neoplastic transformation. The morphological changes induced by TPA were examined by phase contrast and fluorescence microscopy. TPA treatment caused rounding up of cells and loss of adhesion to either fibronectin or laminin substrata. Cytoskeletal actin was redistributed from orientated stress fibre bundles to a perinuclear circumferential arrangement. This was accompanied by a progressive reduction in the number of vinculin-containing contacts with accumulation of vinculin in punctate spots in the perinuclear region. These altered membrane-cytoskeletal interactions induced by TPA are entirely reversible and mimic epigenetic changes which occur during tumour progression.

Composition and organization of cell-substratum contacts in normal and neoplastic renal epithelium.

We have investigated the molecular basis of the organization of cell-substratum contact in normal and neoplastic renal epithelium. The several components of focal contacts and non-collagenous basement membrane glycoproteins have been identified by antibodies, detected by immunofluorescence and viewed by laser scanning microscopy. Tubular epithelial cells grown on glass coverslips expressed laminin at the cell periphery. Co-localized with laminin were receptors of the beta 1 integrin class, and the cytoplasmic plaque proteins vinculin and talin. When basement membrane glycoproteins laminin or fibronectin were exogenously supplied by growing cells on coated coverslips, the vinculin-, talin- and integrin-containing contacts became organized into linear arrays with intervening free cell membranes. Under these conditions the actin cytoskeleton became highly organized. By contrast some tumour cells showed a reduction in focal contact molecules and a failure to organize these structures in response to laminin or fibronectin. This loss of cell matrix interaction may be important during the progression of renal tumours.

Epithelial cell type, clinical behaviour and AgNOR counts in thymic epithelial tumours.

The relationship between epithelial cell type, clinical behaviour and number of nucleolar organiser regions (AgNORs) was investigated in 37 thymomas and three thymic carcinomas. The thymomas were classified according to epithelial cell morphology as cortical (16 cases), medullary (8 cases) or mixed (13 cases). Seven cortical tumours had infiltrated the capsule or adjacent structures at the time of operation, whereas only one medullary and two mixed tumours showed evidence of invasion, the differences being statistically significant (P less than 0.01). None of the patients with medullary thymoma had myasthenia gravis, but there was a significantly higher incidence (P less than 0.001) among those with cortical or mixed tumours (six and three cases respectively). The mean AgNOR count for medullary tumours was 1.56, compared with 2.22 and 2.06 for cortical and mixed tumours. Although the counts for medullary tumours were significantly lower than for the other two types (P less than 0.01), there was considerable overlap. The mean count for the carcinomas was 4.94--significantly higher than for the thymomas (P less than 0.01)--but again overlap was considerable. No relationship was demonstrable between AgNOR counts, clinical stage, incidence of myasthenia or recurrence. It is concluded that although classification of thymomas based on epithelial cell type represents an improvement on previous classifications, it must be applied with caution. Similarly, AgNOR counts may give some indication of malignant potential, but their usefulness in individual cases is doubtful.

Uterus-like mass of the ovary associated with endometrioid carcinoma.

We describe a solid and cystic right ovarian mass removed from a 38-year-old woman. The solid component, which had a central cavity lined by endometriotic tissue and surrounded by a thick muscle wall, strongly resembled a miniature uterus. The contiguous cystic mass was an endometrioid carcinoma. We review the literature and discuss the theories of histogenesis of uterus-like ovarian masses.