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Surface immunoglobulin (sIg) light chain analysis of peripheral blood lymphocytes (PBL) from 63 patients with non-Hodgkin's lymphoma (NHL) was performed to determine the ratio of kappa-bearing lymphocytes to lambda-bearing lymphocytes (kappa/lambda ratio). In 43% an abnormal kappa/lambda ratio was detected, implying the presence of a malignant clone in the peripheral blood (clonal excess). In 67% of cases with an abnormal kappa/lambda ratio, the absolute lymphocyte count was within normal limits and 20% did not have morphologic bone marrow involvement. Light chain analysis of bone marrow aspirates was performed in three of four patients with a circulating clone and normal bone marrow morphology. All three patients had abnormal bone marrow aspirate kappa/lambda ratios. The presence of a circulating clone was associated with morphologic bone marrow involvement (P less than 0.05). Nine patients with documented B-cell NHL were followed with repeated examinations. The presence of a circulating clone persisted in two patients refractory to therapy and in two patients otherwise believed to be in remission. Conversion to an abnormal kappa/lambda ratio occurred in two patients coincident with the development of new bone marrow involvement and in a third patient prior to the onset of frank leukemia. In three instances, the PBL light chain analyses remained within normal limits in patients with stable lymphadenopathy. The kappa/lambda ratio returned to normal in one patient responding to treatment with a partial remission, and remained within normal limits despite progression of lymphadenopathy in one patient, and local disease recurrence in another patient. These findings suggest that the detection of a circulating clone by sIg light chain analysis may be useful as a noninvasive approach to identify disseminated disease activity unsuspected on the basis of morphologic evaluations, but may not reflect the presence, progression, or recurrence of localized tissue lesions.

Murine monoclonal antibodies (MoAbs) were produced against a rat medullary thyroid carcinoma to identify neuroendocrine differentiation antigens. One of these antibodies (1D4) identified a novel 62- to 69-kDa antigen expressed by subsets of immune system epithelial and neuroendocrine cells. This antigen is expressed by distinct subsets of thymic epithelial and splenic reticular cells and is shared by discrete subsets of anterior pituitary and thyroid neuroendocrine cells. In the thymus, 1D4 expression identified a unique subset of stellate-shaped Ia+ medullary epithelial cells which did not react with thymosin alpha-1 antisera nor with the MoAb A2B5 specific for a GQ ganglioside expressed by thymic hormone-producing cells. The availability of the 1D4 MoAb should facilitate further characterization of 1D4+ immune system epithelial cells and may advance our understanding of neuroendocrine-immune system interactions.

The murine 96.5 monoclonal antimelanoma antibody (MoAb) was labeled with In-111, and 1-20 mg were administered to 21 patients who had proved or suspected melanoma metastases. One patient was studied twice. In four patients, unlabeled 96.5 MoAb was administered prior to the radiopharmaceutical. All of the patients tolerated the procedure without toxicity regardless of the mass of MoAb administered. The scans were interpreted by two observers, one with full knowledge, the other with no knowledge of the cases. Increasing the MoAb mass or preinfusing unlabeled MoAb prior to the administration of In-111 MoAb resulted in a prolongation of the serum half time, and appeared to improve tumor detection. Lesions were best seen at 72 hours after infusion or later. In all patients who had metastatic disease, at least one tumor site was apparent. Fifty-six per cent of known lesions 1.5 cm or greater in size were detected by the physician who had knowledge of the cases when data from all doses were considered. There were eight lesions detected that were not suspected in the workup of the patient. When these are included, the detection rate rises to 61%. Forty-nine per cent were detected by the other physician. Subtraction techniques were not employed. Lesions were often better seen with single photon emission computed tomography than with planar imaging techniques. The 96.5 In-111 MoAb appears to have utility for the detection of metastatic melanoma. Further clinical evaluation of 96.5 In-111 MoAb is warranted.

A diagnosis of chronic lymphocytic leukemia (CLL) was made in 81 patients referred for peripheral blood lymphocyte typing (PBL). A retrospective review was undertaken to see if correlations existed between surface marker phenotype-determined subclasses and clinical features. Surface markers utilized were surface immunoglobulin (sIg), sheep erythrocyte receptor (E), 65,000-dalton human T lymphocyte antigen (T65), Ia antigen, and for sIg+ cells, heavy and light chains. All patients were Ia+. Cells of 70% of patients were sIg+ E- T65+ Ia+, and the clinical heterogeneity was that of classical CLL. Eight of the nine patients with sIg+ E- T65- Ia+ cells had a paraprotein. The sIg- E+ T65+ Ia+ phenotype represented classical T cell CLL. Three of the five patients in the sEg- E- T65+ Ia+ group had significant albuminuria, and two had nephrotic-range proteinuria. Use of additional monoclonal antibodies to B cell surface antigens should further subclassify CLL and other lymphoproliferative disorders. Interesting clinical correlations with certain phenotypic subclasses do exist, and further subclassification and long-term follow-up may yield correlations between phenotypes and prognosis.