Gastrointestinal autonomic nerve tumors. 'Plexosarcomas'.

Four plexosarcomas (gastrointestinal autonomic nerve tumors) characterized by light microscopic, immunocytochemical, and ultrastructural examination, including immunoelectron microscopy in one case, are described. The four neoplasms occurred in the small intestine (duodenum, two; jejunum, one; and ileum, one) and they had an aggressive course with either local or distant metastases. The light-microscopic patterns varied from epithelioid and organoid to spindle cells, mimicking endocrine and sarcomatous neoplasms. Ultrastructurally, these tumors exhibited interdigitating cytoplasmic processes that contained scattered aggregates of membrane-bound granules varying in size from 100 to 300 nm intermixed with empty vesicles and numerous diffusely distributed intermediate filaments. Basal lamina covering cell surfaces, attachment plaques, and myofilaments, as expected in smooth-muscle tumors, were not identified, and diffusely distributed membrane-bound granules, as seen in paragangliomas and carcinoid tumors, were also absent. By immunocytochemistry, the tumors were intensely positive for vimentin and neuron-specific enolase and focally positive for neurofilaments and synaptophysin. In addition, three tumors were S100 protein positive and one stained for vasoactive intestinal peptide. Similar positive immunocytochemical reactions were identified in normal enteric plexus. It is essential to recognize plexosarcomas, which are invariably accompanied by aggressive clinical behavior, in spite of a seemingly benign, mitotically inactive light-microscopic appearance in most instances. Ultrastructural examination can readily separate plexosarcomas from paragangliomas and other sarcomatous and endocrine neoplasms.

Neuroendocrine differentiation in prostatic carcinomas. A retrospective autopsy study.

Neuroendocrine differentiation in prostatic neoplasms has in the past been considered extremely uncommon. The histologic neuroendocrine patterns reported previously vary from small cell to carcinoidlike to mixed adenocarcinoma--small cell or carcinoid. The majority of the tumors reported are of the mixed variety. We reviewed 2648 autopsies, revealing 69 prostatic carcinomas, eight with neuroendocrine differentiation (five mixed adenocarcinoma--small-cell carcinoma, two "pure" small cell, and one "pure" carcinoidlike). The mean patient age was 69.5 years. One patient presented with markedly elevated serum corticotropin and another was severely hypercalcemic with elevated serum parathyroid hormone level. Three neoplasms were incidental autopsy findings. The mean survival time, after diagnosis, was 19 months for the other patients. Three of the cases were examined ultrastructurally and showed cytoplasmic processes containing membrane-bound granules in the neuroendocrine component. The areas with neuroendocrine differentiation were positive for markers as follows: neuron-specific enolase, seven of eight; prostate-specific antigen (PSA), none of eight; chromogranin A, seven of eight; synaptophysin, four of eight; and calcitonin, four of eight. Those neoplasms mixed with an adenocarcinoma component showed well-defined PSA positivity in the glandular elements. This study suggests that neuroendocrine differentiation in prostatic neoplasms may be more common than previously thought. Often, the areas with neuroendocrine differentiation are considered to represent poorly differentiated adenocarcinoma. It is important to recognize neuroendocrine components in prostatic carcinomas owing to prognostic and potential therapeutic implications.

Morphologic alterations of the proximal tubules in light chain-related renal disease.

Previous studies from our laboratory have shown that human immunoglobulin light chains (LC) can be toxic to the epithelium of the rat proximal tubule. To examine the toxicity of monoclonal LC's in man, 11 kidney specimens (EXP group) obtained from patients with monotypical LC-related renal disease (7 lambda, 4 kappa), documented by the presence of monoclonal LC's in the serum or urine and in the tissue, were examined by light, immunofluorescence, electron, and immunoelectron microscopy. This EXP group had monotypical LC deposition in the tubules and/or the glomeruli and did not have evidence of intraluminal LC precipitation and cast formation, which alters tubule morphology. A control group (CON; N = 12) of kidney specimens was obtained from patients who had proteinuria greater than 2.5 g/24 hr and mean age (49 +/- 4 vs. 59 +/- 3 years; P = NS), serum creatinine concentration (2.4 +/- 0.5 vs. 3.2 +/- 1.5 mg/dl; P = NS) and creatinine clearance (65 +/- 13 vs. 63 +/- 12 ml/min; P = NS) similar to the EXP group. All of the EXP specimens demonstrated varying degrees of proximal tubule damage, manifested by cell vacuolation, desquamation, loss of the luminal brush border, and, often, coagulation necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital toxoplasmosis in an infant with hydrops fetalis.

We have described an infant born with severe hydrops fetalis due to congenital toxoplasmosis. Although uncommon, toxoplasmosis should be considered in the differential diagnosis of hydrops fetalis, particularly when the preliminary clinical work-up suggests a nonimmunologic basis for the hydrops. Although the clinical outcome in an infant as severely affected as this one will remain poor, the therapy for toxoplasmosis has improved over the years, and with quick diagnosis of the disease, a less severely affected infant may have a better prognosis.

S-100 protein expression by primary and metastatic adenocarcinomas.

S-100 protein has been used as a marker of various lesions, including peripheral nerve sheath, cartilaginous and salivary gland tumors, chordomas, histiocytosis X, and melanomas, among others. The list of neoplasms that can express S-100 protein continues to expand. It has been suggested that staining for S-100 protein may be of aid in the differential diagnosis of amelanotic melanoma versus poorly differentiated tumors. Three hundred fifty primary and metastatic adenocarcinomas from various sites were immunostained for S-100 protein with the use of a commercially available polyclonal antibody. Forty-two percent of the adenocarcinomas tested expressed S-100 protein to varying degrees. The relative incidence of S-100-positive tumors varied with the primary sites, some expressing S-100 protein more often than others. A primary neoplasm able to express S-100 protein was usually associated with metastatic foci also expressing this marker. However, occasionally, a primary S-100-positive tumor was associated with metastasis that lacked expression of S-100. This study emphasizes the importance of testing for a panel of tumor markers in the evaluation of poorly differentiated tumors and cautions on possible difficulties that may arise in the interpretation of immunocytochemistry results.

Ultrastructural immunolabeling in renal diseases. Past, present and future expectations.

The use of immunoelectron microscopy in the evaluation of renal diseases represents a valuable addition to existing techniques. The ability to immunolabel immune-complex deposits for light- and heavy-chain determinants, and complement fractions virtually eliminates the need for traditional immunofluorescence. One of the main advantages of performing immunoelectron microscopy relates to the fact that immunologic events can be adequately correlated morphologically with the degree and type of tissue reactions in the various renal compartments. Immunopathogenetic mechanisms can be clearly evaluated with this technique. The need to submit specimens in different fixatives is eliminated and all diagnostic modalities can be performed on a single fragment of tissue. The examination of the thick sections prepared from plastic-embedded tissue for survey provides excellent material for interpretation of findings at the light-microscopic level. These sections can be stained with hematoxylin/eosin, trichrome, silver methenamine and PAS stains with excellent results. The time and resources needed for processing renal biopsies can be significantly reduced by utilizing the proposed methodology. Likewise, interpretation of results may benefit from utilization of the same fragment for all diagnostic modalities.

Ultrastructural immunolabeling in the diagnosis of light-chain-related renal disease.

Renal tissue from eight patients with light-chain deposition disease (LCDD) was immunolabeled for electron microscopy by a postembedding indirect immunogold staining procedure, using anti-kappa and anti-lambda antibodies. This technique provided an exact immunomorphological method to confirm the presence of monotypical light chains in glomeruli, tubules, and vessels. In two cases, it served to prove monotypical light-chain deposition which was not clear upon examination of sections stained for kappa and lambda light chains at the light microscopic level, using PAP or immunofluorescence methods. Three cases of amyloid nephropathy, in which the amyloid deposits stained for monospecific light chains and were immunolabeled ultrastructurally, are also described. LCDD manifests with a variety of morphological patterns in the kidney and the pathological definition of this entity has been difficult. Ultrastructural immunolabeling is a useful method to supplement existing techniques in the diagnosis of LCDD and related conditions. One outstanding feature of the postembedding technique is the ability to examine fixed and preserved renal tissue for the presence of light chains on a retrospective basis.