Third ventricular primary cerebral neuroblastoma. Electron-microscopic and immunohistochemical study

A case of third ventricular primary cerebral neuroblastoma with secondary hydrocephalus is reported. Light microscopy showed a cell pattern that resembled either ependymoma or oligodendroglioma. The tumor was confirmed to be neuroblastoma by electron microscopy and immunohistochemistry. Immunoperoxidase staining was positive for neuron-specific enolase and negative for glial fibrillary acidic protein.     

Hemodialysis-associated amyloidosis of bone of beta-2 microglobulin origin

Summary A case of hemodialysis-associated amyloidosis in a patient who had been on hemodialysis for 10 years is described. Bone lesions were found in the humeral heads, carpal bones, and femoral heads and necks. Specimens obtained from the pathologically fractured left femoral neck revealed amyloid deposits histologically. Immunoperoxidase staining for beta-2 microglobulin was positive in the amyloid at the light-microscopic level. We reconfirmed that bone lesions associated with long-term hemodialysis are manifestations of amyloidosis of beta-2 microglobulin origin. Hemodialysis-associated amyloidosis should be considered in the treatment of long-term hemodialysis patients.     

Signet-ring-cell carcinoma of the prostate. Electron-microscopic and immunohistochemical studies of eight cases

Primary signet-ring-cell carcinoma of the prostate is extremely rare. We report eight patients with prostatic adenocarcinomas containing significant numbers of signet-ring cells, one of whom presented initially with supraclavicular lymph node metastasis. Patient ages ranged from 50 to 80 years (mean, 67.5). None of the patients had received any form of therapy before biopsy or surgery. All patients presented with advanced disease (five with stage C and three with stage D). All tumors were poorly differentiated adenocarcinomas, M.D. Anderson Hospital system grade IV, Gleason's combined score of 9 or 10. The signet-ring cells were negative for neutral and acid mucins but immunoreactive for prostatic-specific antigen and prostatic acid phosphatase. Ultrastructurally, the signet-ring-cell appearance resulted either from the presence of intracytoplasmic lumina or from vacuoles. Signet-ring cells were also present at the metastatic sites. We conclude that (a) signet-ring-cell carcinoma of the prostate is a variant of poorly differentiated adenocarcinoma of the prostate; and (b) when a metastatic signet-ring-cell carcinoma with negative intracytoplasmic mucin is identified, a prostatic origin should be considered, and prostatic-specific antigen and prostatic acid phosphatase immunostaining should be performed.     

Laryngeal amyloidosis: a clinicopathologic and immunohistochemical review.

The clinical nature of laryngeal amyloidosis has not been well established, and the natural history of the disease remains a controversial matter. To address these issues, we reviewed the clinicopathologic and immunohistochemical features of 22 cases (11 men and 11 women; mean age, 56 years) of laryngeal amyloidosis. Hoarseness was the most common symptom, and the most frequent site affected was the false vocal cords. Six patients had concomitant tracheal amyloidosis. Paraffin blocks were available for immunostaining in 20 cases. Nineteen cases were positive for amyloid P component. lambda-Light chains were detected in 12 cases and kappa-light chains in 5; three cases did not show definite light-chain staining. Ten patients underwent repeated operations for persistent or recurrent respiratory tract disease. One patient died of progressive tracheobronchial amyloidosis, but systemic amyloidosis did not develop in any of the patients. Laryngeal amyloidosis is a form of localized amyloidosis characterized by monoclonal light-chain deposition. Recurrent respiratory tract disease is not uncommon, but the usual clinical course is relatively benign.     

Primary localized amyloidosis of the bladder: an immunohistochemical study of a case.

We report a case of primary localized amyloidosis of the bladder causing renal failure. Immunohistochemically, amyloid fibril protein originated from the lambda type light chain of immunoglobulin.     

Collagen-binding affinity of beta-2-microglobulin, a preprotein of hemodialysis-associated amyloidosis

beta 2-Microglobulin (B2M) is the amyloid preprotein that accumulates in amyloid osteoarthropathy associated with hemodialysis. To elucidate the mechanism of such amyloidogenesis, we investigated the interaction between B2M and collagen in vitro by solid-phase enzyme immunoassay. Soluble collagens which had been solidified on plastic plates were allowed to react sequentially with B2M, peroxidase-conjugated antibody to B2M, and the substrate. The collagen-binding activity was dependent on the concentration of B2M and collagen, respectively. These results suggest that the collagen-binding affinity of B2M plays an important role in amyloidogenesis.     

Proliferative myositis. An immunohistochemical and ultrastructural study

We studied four cases of proliferative myositis by the avidin-biotin-peroxidase complex technique, using a panel of 12 antibodies, and by electron microscopy. The aim was to clarify the nature of their constituent cells, specifically the giant ganglion-like cells and spindle cells, and to discuss the implications for histogenesis. In all cases, both cell types showed positive cytoplasmic staining with antibodies to vimentin, actin (C4), and alpha-smooth muscle actin-1, but in only one was there positive staining with desmin. No staining was obtained with factor XIIIa, muramidase, alpha-1-antitrypsin, myoglobin, S-100 protein, CAM 5.2, factor VIII-related antigen, or neuron-specific enolase. By electron microscopy, both types of cells were seen to contain numerous thin filaments, dense bodies, coated and pinocytotic vesicles, active and dilated rough endoplasmic reticulum, few microvilli, and incomplete desmosomal junctions. Our findings imply a myofibroblastic nature for the giant ganglion-like cells and spindle cells. Our observations also support the hypothesis that they are derived from a pericytic cell.     

Clinicopathologic and immunohistochemical study of intraoral mucoepidermoid carcinoma.

OBJECTIVE: The purpose of this study is to assess the clinicopathologic and immunohistochemical features of intraoral mucoepidermoid carcinomas and its relationship with the prognosis. STUDY DESIGN AND SETTING: From 1953 to 1993, 27 patients with intraoral mucoepidermoid carcinomas surgically treated were selected for this study. Clinical data were obtained from the medical records, the microscopic slides were reviewed, the tumors were graded, and immunohistochemical analysis for p53, PCNA, cerbB-2, and CEA were carried out. RESULTS: The tumors were more frequent in patients between 40 and 60 years of age (40.7%), without gender predilection. Hard palate was the most common site with 13 cases (48%). T2 was the more frequent stage (48%) and 2 patients (7.4%) were staged as N+. Most tumors (48%) were classified as low grade of malignancy. The expression of PCNA was associated to high-grade tumors (P = .00610) and c-erbB-2 to low grade tumors (P = .03958). No recurrence was noted in most of the cases (22 cases, 81.5%). Three cases (11.1%), however, showed local recurrence and 2 patients (7.4%) died because of the disease. The analysis of the overall survival rate showed that male patients (P = .04249), stage N (P = .05948), high grade of malignancy (P = .0009), strong expression of PCNA (P = .09128), and weak expression of c-erbB-2 (P = .03334) had the lowest survival rates. CONCLUSION: Our results showed that patients with intraoral mucoepidermoid carcinoma had a reduced survival expectation if they were of the male gender, with regional metastasis, high grade of malignancy, strong expression of PCNA and weak expression of c-erbB-2. EBM rating: C-4.     

Glycosaminoglycans enhance the trifluoroethanol-induced extension of beta 2-microglobulin-related amyloid fibrils at a neutral pH

beta(2)-Microglobulin-related (A beta 2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis, and beta(2)-microglobulin is a major structural component of A beta 2M amyloid fibrils. Several biologic molecules inhibiting the depolymerization of A beta 2M amyloid fibrils at a neutral pH were found recently. The effect of trifluoroethanol and glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was investigated with the use of fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at concentrations of up to 20% (vol/vol) caused fibril extension of heparin-stabilized seeds, inducing a subtle change in the tertiary structure of beta(2)-microglobulin and stabilizing the fibrils at a neutral pH. This extension reaction followed a first-order kinetic model. In addition, some GAG, especially heparin, dose-dependently enhanced the fibril extension. These results suggest that some GAG, especially heparin, may bind to the fibrils and enhance their deposition in vivo. Thus, the experimental system described here should be useful to search for the factors that accelerate A beta 2M amyloid deposition in vivo. In addition, the interference of the binding of GAG to A beta 2M amyloid fibrils may be an attractive therapeutic modality.     

Immunoproliferative small-intestinal disease. An immunohistochemical study

We performed a detailed histological and immunohistological study on both fresh-frozen and paraffin-embedded tissue from full-thickness jejunal biopsy specimens taken from three patients with immunoproliferative small-intestinal disease (IPSID). In all three patients, the mucosal infiltrate consisted of "centrocyte-like" (CCL) cells forming lymphoepithelial lesions and plasma cells. In one patient, the mucosal infiltrate was strikingly follicular. Immunohistochemistry showed alpha 1 heavy chain, but no light chain, in the perinuclear space and cytoplasm of the CCL cells and in the plasma cells. In two patients, the plasma cells (but not the CCL cells) also contained alpha 2 heavy chain. In the case showing a follicular pattern, the extrafollicular CCL cells and most of the cells within the mucosal follicles expressed alpha 1 heavy chain, but a minor and variable population of cells expressed polytypic IgM. The dendritic reticulum cells stained for alpha 1 (but not alpha 2) heavy chain, mu chain, and both light chains. In all cases, the CCL cells did not stain for common acute lymphoblastic leukaemia antigen (CALLA); in the follicles, CALLA negative cells displaced a residual CALLA-positive population to the periphery and merged with the CALLA negative cells outside the follicles. These findings confirm the homology between IPSID and low-grade B-cell "Western" lymphomas arising in mucosa-associated lymphoid tissue; they suggest that the follicular pattern sometimes seen in these lymphomas is caused by selective colonization of reactive follicles by CCL tumor cells.     

Nephropathia epidemica: immunohistochemical study of pathogenesis.

Renal immunohistochemistry was studied in 21 patients with Nephropathia epidemica, a benign hemorrhagic fever endemic in northern Europe. Between days 4 and 25 after the onset of fever, scanty but distinct deposits containing immunoglobulins and C3 were detected in glomeruli and tubules. The occurrence of deposits was verified with electron microscopy. It is concluded that an immune complex mechanism plays a part in the pathogenesis of this disease. It is also evident that the febrile period coincides with the presence of immune complexes in the circulation.     

Filiform large-cell lymphomas. An ultrastructural and immunohistochemical study

Ten cases of "undifferentiated" large-cell tumors were ultrastructurally characterized by cells with abundant filiform cytoplasmic projections without intercellular junctions. These cases were studied by means of the avidin-biotin-peroxidase complex (ABC) technique applied to formalin-fixed, paraffin-embedded sections using antibodies against high- and low-molecular weight keratins (Ker), vimentin (Vi), epithelial membrane antigen (EMA), S-100 protein, leucocyte common antigen (LCA), kappa (K) and lambda (L) light chains, Leu-M1, lysozyme (Ly), alpha-1 antitrypsin (A1AT) and alpha-1 antichymotrypsin (A1ACT). All 10 cases were negative for Ker and EMA but positive for Vi. S-100 was present only in scattered dendritic cells. LCA was identified in seven cases. In the three LCA-negative cases, two stained for Leu-M1, and one of these also showed intracytoplasmic L; one was negative for all markers but Vi. None of the tumors showed any significant staining for Ly, A1AT, or A1ACT. Our findings indicate that these tumors are nonepithelial and nonneuroectodermal, and that they are best classified as non-Hodgkin's lymphomas. The possibility that some of the filiform large-cell lymphomas may be derived from dendritic reticular cells cannot be excluded.     

Serum beta-2-microglobulin levels in urological cancer.

Serum beta-2-microglobulin levels were measured in patients with renal, vesical and prostatic cancer. Measurements were made only on samples with a serum creatinine less than or equal to 105 mumol./l. to eliminate the possibility of elevated beta-2-microglobulin being a result of impaired renal function. This criterion eliminated 28 to 50 per cent of the patients with bladder cancer and 73 per cent of those who had undergone nephrectomy for renal carcinoma, which, obviously, limits the value of beta-2-microglobulin measurement for the surveillance in these cancers. Beta-2-microglobulin values in patients with prostatic cancer were seldom increased to more than 3.0 mg./l. In bladder cancer patients with normal serum creatinine the frequency of an elevated serum beta-2-microglobulin increased with the increase in tumor stage.     

Middle East lymphoma and alpha-chain disease. An immunohistochemical study.

An immunoperoxidase study of the small intestinal mucosa of three patients with alpha-chain disease showed heavy infiltration of the mucosa by plasma cells containing alpha-heavy chain and J-chain but no light chains. An additional band-like and nodular mucosal infiltrate was also present and consisted of cells showing no evidence of cytoplasmic immunoglobulin synthesis. The cells comprising this infiltrate invaded and destroyed intestinal crypts, and immunoperoxidase staining showed them to be sharply distinct from the alpha-chain-containing plasma cells. In two cases of Middle East lymphoma, immunohistochemistry revealed a normal plasma cell population in the lamina propria of the small intestine. These results show that alpha-chain disease can be diagnosed in routine paraffin sections which should permit clarification of its true incidence in Middle East lymphoma. The demonstration of sharp distinction between the two types of mucosal infiltrate in alpha-chain disease is in contrast to previous immunofluorescence results and enables more ready identification of mucosal changes that may be important in the management of the disease.