Although conferring a grave prognosis in patients with malignant lymphoma, high levels of serum lactic dehydrogenase (LDH) are usually not seen in patients with multiple myeloma, a more indolent tumor composed mainly of B cells in their terminal stage of differentiation. Thus, only 2 of 118 patients in earlier phases of myeloma showed marked LDH elevations to more than 500 U/L, whereas such abnormalities were present in 12 of 64 patients with advanced disease progressing despite treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD) (median LDH level, 700 U/L). High LDH levels were associated with high serum levels of beta-2-microglobulin, hypercalcemia, extraosseous disease features, a short preceding clinical course as well as a short subsequent survival time. A poor prognosis was also noted in patients with lower LDH in whom marked increments were induced by high-dose chemotherapy; thus, LDH elevations to greater than 300 U/L present before or found after high-dose cytotoxic therapy were observed in about 50% of patients with VAD-resistant myeloma and define a new clinical entity with features of extraosseous disease and an unusually aggressive course ("high-grade myeloma"). The shorter survival of newly diagnosed patients with high-normal compared with those with low-normal LDH levels (less than 200 U/L), regardless of tumor mass, suggests the presence in some patients of a tumor subpopulation with high LDH production that escapes growth control with standard treatment. Staging of multiple myeloma should therefore include measurements of serum LDH levels in addition to beta-2-microglobulin analysis and tumor mass estimation.

High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma

The nuclear DNA content of 44 pituitary, 49 thyroid, 54 parathyroid, and 17 adrenal adenomas was analyzed from paraffin-embedded tissue with flow cytometry. Interpretable histograms of good quality (CV less than 7%, mean CV, 4%) were obtained in 96% of the cases. Unequivocal evidence of DNA aneuploidy was found in 29% of pituitary, 25% of thyroid, 35% of parathyroid, and in 53% of adrenal adenomas. Excluding the multiploid (N = 2) and tetraploid adenomas (N = 5), the DNA indices of aneuploid adenomas were generally small (mean, 1.34). Patients with a diploid thyroid or parathyroid adenoma had a lower mean age at diagnosis than patients with a nondiploid adenoma. None of the adenomas gave rise to metastases after conservative surgery. It is concluded that DNA aneuploidy is common in endocrine adenomas and that the presence of DNA aneuploidy is not incompatible with a benign histologic diagnosis. The usefulness of DNA aneuploidy as a conclusive sign of malignancy in clinical practice is questioned.

DNA aneuploidy in adenomas of endocrine organs.

The nuclear DNA content of 67 follicular adenomas and 7 adenomatous goiters was determined by flow cytometry. The DNA analysis was done with the use of paraffin-embedded tissue, but in 14 cases of follicular adenoma fresh material obtained by fine needle aspiration biopsy was also available. An abnormal DNA stemline was found in 27% (18/67) of the adenomas and in 1 (14%) of the adenomatous goiters. Four (29%) of the 14 adenomas analyzed from fresh samples were aneuploid. In none of the 12 aneuploid or 40 diploid adenomas followed for more than 5 years (mean, 7.2 years) did distant metastases develop after surgical removal of the adenoma. The paraffin blocks of cases with DNA aneuploidy were sectioned subserially at 1-mm intervals, but none of these tumors showed invasion into the capsule or blood vessels. It is concluded that DNA aneuploidy is common in histologically benign follicular adenomas of the thyroid, and that DNA aneuploidy does not appear to be associated with adverse prognosis in follicular adenomas if the tumor is surgically removed.

DNA aneuploidy in follicular adenomas of the thyroid gland.

The authors conducted a retrospective analysis with 5- to 30-year follow-up on 109 patients in order to determine the optimum management of nonmedullary thyroid cancer. Results of total thyroidectomy were compared to partial thyroidectomy, among patients well matched for prognostic indicators. No differences in cancer mortality or recurrence rates were evident. However, there were significantly more complications when total thyroidectomy was employed. In view of these results, partial thyroidectomy is recommended as the treatment of choice for nonmedullary thyroid cancer.

Operative strategy for thyroid cancer. Is total thyroidectomy worth the price

Cellular DNA content was measured using a novel flow cytometric method to analyze paraffin-embedded tissue blocks from 125 patients with differentiated thyroid cancer. DNA aneuploidy was found in 20 (24%) of the 82 papillary, 20 (56%) of the 36 follicular, and in four (57%) of the seven medullary carcinomas. Aneuploidy was found to be more common in the elderly (P less than 0.002), in moderately and poorly differentiated carcinomas (P less than 0.004), and in tumors infiltrating beyond the thyroid capsule (P less than 0.03). Patients with an aneuploid tumor had less favorable cumulative survival (P less than 0.0001) than patients with diploid cancer. However, in papillary and follicular carcinomas, multivariate analysis using stepwise Cox model showed age at diagnosis, follicular type, and tumor invasion beyond the thyroid capsule to be more important independent prognostic factors. Increasing probability of DNA aneuploidy with increasing age explains partially why prognosis of differentiated thyroid carcinoma is poor in older patients.

Influence of cellular DNA content on survival in differentiated thyroid cancer.

Heterogeneity of non-Hodgkin's lymphoma probed by nucleic acid cytometry

• Mechanically dispersed cell suspensions from 23 thyroid lesions were studied by acridine orange flow cytometry. Eight of 14 carcinomas (three papillary, two medullary, two Hurthle cell, and one follicular) manifested abnormal DNA indices ranging from 0.6 to 2.0. Six carcinomas (four papillary and two medullary) were diploid. Four patients having papillary carcinomas with diploid DNA content were young women whose clinical course of disease was indolent. Three papillary carcinomas with abnormal DNA content were found in older men with clinically aggressive disease. One benign adenomatoid nodule displayed a small population with a low-degree hyperdiploid stemline (DNA index = 1.1) with low proliferative activity. Differentiation between clinically indolent and aggressive carcinomas may be possible by nuclear DNA determination, but further work is needed to determine the importance of proliferative activity in thyroid carcinoma. (Arch Otolaryngol1985;111:34-38)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=otol&articleId=612007&pdfFileName=archotol_111_1_008.pdf

DNA flow cytometry of thyroid neoplasms.

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Heterogeneity of non-Hodgkin's lymphoma probed by nucleic acid cytometry

DNA flow cytometry of thyroid neoplasms.