Epstein-Barr virus-associated lymphoproliferative disorder. Applications of immunoperoxidase and molecular biologic techniques.

A 17-year-old boy with fever and cervical lymphadenopathy developed multiple-organ failure and died three weeks after hospital admission. A lymph node biopsy specimen demonstrated a florid immunoblastic infiltrate that was suspicious for a malignant lymphoma. By using immunoperoxidase and molecular biologic techniques, evidence was presented for an Epstein-Barr virus-associated lymphoproliferative disorder.

Use of phorbol-12,13-dibutyrate as a mitogen in the cytogenetic analysis of tumors with low mitotic indexes.

Solid tumors, particularly those involving the colon, breast, and lung, are the most common tumors in humans. However, many technical difficulties exist in obtaining analyzable chromosomes from these tumors, including the inability to stimulate cell division. Phorbol-12,13-dibutyrate (PDBu) is a tumor promoter that activates a variety of cellular responses, including proliferation. Using flow cytometry, we have demonstrated that PDBu acts as a mitogen in primary cultures of colon tumor cells. Based on these results, we developed a short-term culture technique that greatly improves the yield of analyzable metaphases from colon tumors. Stimulated cultures consistently contained at least ten times more metaphases than unstimulated cultures, and chromosome morphology was improved. By modifying this technique with the addition of the calcium ionophore A23187, we have successfully obtained analyzable chromosomes from the peripheral blood of normal individuals, chronic lymphocytic leukemia patients, and a nodular small cell lymphoma patient. These results demonstrate that mitogenic stimulation by PDBu is a valuable technique in the cytogenetic analysis of colon tumors. By using PDBu alone or in combination with other agents, this technique may also be applicable to many other tumors that are difficult to karyotype because of an inability to obtain mitoses.

Fine needle aspiration biopsy of the thyroid. Differential diagnosis by videoplan image analysis.

Fine needle aspiration biopsy of cold thyroid nodules has become increasingly popular in determining neoplastic versus nonneoplastic conditions. The differential diagnosis between follicular adenoma and low-grade follicular carcinoma has not been consistently attainable, however; adenomatous goiter also may present problems in diagnosis, while papillary carcinoma seldom proves to be a difficult diagnosis. Image analysis, utilizing the Videoplan image analysis system, was performed on fine needle aspiration biopsy smears from these four types of nodules. The nuclear area, maximum diameter, minimal diameter and approximation to a circle were determined for 25 randomly selected cells with intact nuclei in each smear. These values were calculated with a range and standard deviation and were graphed for each parameter by case category. Cytoplasmic measurements could not be performed due to the absence of definite cytoplasmic boundaries. There was no significant difference in mean nuclear area between follicular adenoma, follicular carcinoma and adenomatous goiter. Papillary carcinoma was the only lesion to show any difference with this single parameter. The mean of maximum and minimum diameter and approximation to a circle were similar for all the types of thyroid masses examined in this study. The Videoplan image analysis system provided an efficient and accurate means of obtaining the nuclear measurements and calculating the statistics. These data illustrate that a differential diagnosis between follicular adenoma, follicular carcinoma and adenomatous goiter, while difficult by light microscopy, is not aided by image analysis of individual cell nuclei.