Paraffin sections of 106 primary thyroid carcinomas were the subject of an immunocytochemical study to determine the density of infiltrates of S-100 protein-positive dendritic/Langerhans cells (LC), lysozyme-positive histiocytes, and LCA-positive lymphocytes. Evidence of dense infiltrates of LCs was found only in the majority of papillary thyroid carcinomas (PCs). The determination of the quantity of LCs proved to be a highly effective means of assessing the prognosis of these tumors. Irrespective of other morphologic and clinical features, no single instance of death resulting from cancer occurred among 23 PCs with dense LC infiltrates (including 6 tumors of stage pT4), while 9 of 53 (17%) of the remaining patients ultimately died from thyroid cancer. On the other hand, the degree of histiocytic and lymphocytic infiltrations was not associated with a distinct biologic behavior neither among PC nor among the remaining thyroid carcinomas. These findings suggest that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor only in the papillary type of thyroid cancer.

To establish an objective basis for therapeutic decisions and follow-up programs in patients with follicular thyroid cancer, the authors developed a prognostic scoring system. The prognostic impact of nine clinical, histologic, and therapeutic parameters was quantified retrospectively based on a multivariate analysis covering 149 patients. The relative relapse risk in follicular thyroid cancer (RR) was 6.8-fold increased in the presence of a moderate when compared with a high degree of histologic tumor differentiation. The RR rose with increasing age of the patient at time of tumor diagnosis by a factor of 1.8 per 20 years. The RR was reduced by a factor of 4.3 after the performance of a neck dissection and by a factor of 2.3 after percutaneous radiation therapy of the neck. The relative mortality risk in follicular thyroid cancer (RM) rose in the absence of a tumor capsule by a factor of 10, in the presence of a moderate compared with a high degree of histologic tumor differentiation by a factor of 5.9, in the presence of distant metastases by a factor of 3.2, and with increasing age of the patient at the time of tumor diagnosis by a factor of 2.2 per 20 years. From these data prognostic indices denoting the individual risk for tumor relapse (IRR index) and tumor mortality (IMR index) were calculated. The indices categorize patients into low-risk, medium-risk, or high-risk groups with regard to tumor relapse and tumor-related death. Consequently, the IRR and IMR indices contribute to select patients with follicular thyroid cancer who need an aggressive form of treatment and an intensive followup program. The indices may also be used for risk stratification in prospective therapy trials. Cancer 67:1903Cancer 67: -1911Cancer 67: ,1991. Accepted for publication October 15, 1990. thyroid cancer runs a benign course when compared with other malignancies,* it decreases the quality of life or becomes fatal in a substantial percentage of patient^.^ It is our conviction and that of others'*4 that implementation of risk-oriented medical care in thyroid cancer based on objective criteria, as revealed by mathematical assessment of prognosis, will both improve prognosis and minimize unnecessary treatment. The mathematical assessment of individual prognosis in diseases has become possible with the development of multivariate rn~dels.~ These models determine prognostic factors and quantify their impact on prognosis. In addition, the models permit the calculation of prognostic indices. These indices determine the relapse or mortality risk of a patient as a function of the individual constellation of prognostic factors.Multivariate analyses of prognostic factors in thyroid cancer have recently been reviewed.6 Among these studies, 1903

Because Langerhans' cells (LC) (CD1a-positive epidermal cells) have been discussed to be involved in the pathogenesis of mycosis fungoides and Sézary syndrome, the authors examined the influence of densities of Langerhans' cells and, concurrently, of other phenotypes retrospectively on survival of 35 patients. Cell densities were assessed on cryostat sections (alkaline phosphatase antialkaline phosphatase-technique) of the respective diagnostic biopsy specimens. Additionally, two clinical parameters (age, stage of disease) were evaluated. CD1a-positive epidermal cells were demonstrated to be the only cell population being significantly associated (P = 0.011) with survival. Death resulting from mycosis fungoides and Sézary syndrome was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers. These results suggest that Langerhans' cells have a significant impact on prognosis of patients with mycosis fungoides and Sézary syndrome. They play an important role in the host defense mechanisms against these lymphomas rather than to favor their progression as proposed recently.

Leu-M1 antigen is a monocyte/granulocyte-related marker known to be consistently expressed in the Reed-Sternberg cells of patients with Hodgkin's disease. Recently, however, the presence of Leu-M1 has also been noted in tumour cells of a variety of non-haematopoietic neoplasms, most of them adenocarcinomas. The biological significance of this aberrant reaction has not been clarified. We have been able to demonstrate marked epithelial Leu-M1 immunoreactivity (greater than 15% tumour cells positively stained) in 24 out of 76 (32%) papillary carcinomas of the thyroid gland (PC). This phenomenon was more frequently observed among PCs at an advanced stage of disease (pT4 vs. pT1-3 and M1 vs M0 p less than 0.05). The degree of epithelial Leu-M1 positivity was also shown to be significantly correlated to the clinical course of PC. Irrespective of other morphological and clinical features, death resulting from cancer occurred 17 times more frequently among PCs with marked Leu-M1 positivity (8/24) when compared with tumours with only slight or absent immunoreactivity (1/52) (p less than 0.00005). These findings suggest that Leu-M1 immunostaining provides significant prognostic information for patients with papillary carcinoma of the thyroid gland.

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