Stromal Fat Content of the Parathyroid Gland TAKAO OBARA,* YOSHIHIDE FUJIMOTO* AND MOTOHIKO AIBA** *Department of Endocrine Surgery and **Department of Surgical Pathology, Tokyo Women's Medical College, Tokyo, Japan Abstract The proportion of stromal fat cells to parenchymal cells in 100 normal parathyroid glands was determined by the image analyzing computer technique. The parathyroid glands were resected at the time of thyroidectomy in 86 patients with thyroid tumors. None of the patients had any evidence of parathyroid dysfunction preoperatively. In the histologic sections of the parathyroid glands, the average percentage of stromal fat cell content was 38%. The percentage of stromal fat cells was correlated with the age and the body constitution of the patients, but the percentages of fat cells varied widely among glands in the given age and body constitution ranges. It was therefore not possible to discriminate a normal parathyroid gland from an abnormal gland solely on the basis of microscopic determination of stromal fat cell content. In the histopathologic examination of resected parathyroid glands, it is of fundamental importance to determine whether a parathyroid gland that appears normal in size is actually normal or hyperplastic, because the exact differentiation between adenoma and hyperplasia based solely on examining an obviously enlarged gland is almost impossible. Most pathologists are accustomed to diagnose normalcy of a given parathyroid gland on the basis not only of size but also of the high percentage of stromal fat cells in histological sections. The normal adult parathyroid has been considered to be composed of approximate- Received July 17, 1990 Address all correspondence and requests for reprints to; TAKAO OBARA, M.D. Department of Endocrine Surgery, Tokyo Women's Medical College, Kawada-cho, 8-1, Shinjukuku, Tokyo, 162, Japan (Telephone number: 03-3353-8111). ly 50% fat cells, and a marked decrease in fat cell content is thought to reflect the endocrine hyperactivity of the gland (Straus and Paloyan, 1969; Roth, 1971; Golden and Kerwin, 1982). Several investigators have questioned the figure of 50% fat cells and have shown that the normal parathyroid gland contains much less fat than hitherto believed (Dekker et al., 1979; Dufour and Wilkerson, 1982; Saffos et al., 1984). However, these studies were based on parathyroid glands taken at autopsy and changes in nutritional and other therapeutic agents in the terminal stage of the patient's illness may have induced the morphological changes in the glands. It would be better to define histologic features of the normal parathyroid gland on the basis of evaluation of the glands surgically respected from patients with normal parathyroid function. Therefore we studied the proportion of fat cells
OBARA et al. in parathyroid glands unintentionally removed at thyroid surgery. Materials and Methods One hundred histologic slides containing a whole section of a parathyroid gland were selected at random from the pathologic files in the Department of Surgical Pathology of Tokyo Women's Medical College. The tissues had been fixed in 10% neutral formalin and routinely processed and embedded in paraffin. Thin sections of the specimens were stained with hematoxylin and eosin and photographed through a microscope. The photographs were printed at 20 times magnification. The distribution of fat tissue in the glands was calculated from a real estimation by means of an image analyzing computer system (MOP-Videplan, Kontron, West Germany). Areas with large blood vessels along with perivascular connective tissue were excluded. These slides were of tissues of 86 patients who were operated on for either benign or malignant thyroid tumors between 1981 and 1986. The clinical and laboratory records of the patients were reviewed. The age of the patients ranged from 10 to 74 years with a mean age of 46. The patients were 20 males and 66 females. Seventy patients had carcinoma of the thyroid and 16 patients had benign thyroid nodules. In all patients preoperative thyroid function was normal without any medication and no other endocrine abnormalities were clinically noted. Body weight, height, and serum levels of calcium, phosphorus, blood urea nitrogen (BUN), and creatinine were tabulated from clinical and laboratory records. The average levels and standard deviations of serum calcium, phosphorus, BUN, and creatinine were 8.9 }0.4mg/100ml, 3.5 }0.5mg/100ml, 14.1 } 2.9mg/100ml, and 1.0 }0.2mg/100ml, respectively. None of the patients had overt parathyroid or renal dysfunction. Results icroscopically, all parathyroid glands mainly comprised parenchymal cells and Table 1. Stromal fat cell content in normal parathyroid glands. Fig. 1. Stromal fat cell content (%) in normal parathyroid glands plotted against age.
STROMAL FAT IN NORMAL PARATHYROID mature fat cells. In each gland, the predominant cells of the parenchyma were chief cells. In only one of the 100 glands, oxyphil cells were present as a minute nodule. The remainder was scattered in the form of small nests or single cells. Most parenchymal cells were arranged in various patterns which reflected the amount of fat cells. No cellular atypism was noted in any of the glands. The average fat cell content and standard deviation in all parathyroid glands was 38.0+20.1%. It was higher in women (39.3%) than in men (33.8%), but the difference was not significant. The percentage of stromal fat cells varied widely (Table 1). Of the 100 glands, 31 showed a fat cell content more than or equal to 50%, while in 30 it was between 30 and 49% and it was less than 30% in 39, in 7 of whom it was 10%. The percentage of fat cells in each gland was plotted against the age of the patient (Figure 1). There was a significant correlation between these two parameters (p=0.029), but the standard error of regression coefficient was 19.31. The percentage of fat cells in the normal parathyroid gland is compared with the body constitution of the patient in Figure 2. The latter was judged by the body fat parameter as defined in the figure legend. The parathyroid fat cell content was also well correlated with the body fat parameter (p=0.0099). Nevertheless, the standard error of regression coefficient was 19.53. The fat cell content was not correlated with the serum level of calcium, phosphorus, BUN or creatinine. In 13 patients, two or three glands were available for estimation of stromal fat cell content (Figure 3). Six of the patients had a similar percentage of fat tissue in each gland. In the remaining seven patients, fat cells were unequally distributed between the two glands. Discussion The fat cell content in the normal parathyroid gland is a matter of concern to pathologists, especially when they are required to tell whether a normal sized Fig. 2. Stromal fat cell content (%) in normal parathyroid glands plotted against grade of obesity. Grade of obesity was calculated by the following formula: Desirable weight=(height-100) ~0.9
OBARA et al. Fig. 3. Distribution of stromal fat cell content among the parathyroid glands of each individual. parathyroid gland is definitely normal or hyperplastic. It has been believed that when the parathyroid gland is in a hyperplastic or hyperactive state the fat cells in the gland decrease with a corresponding increase in the number of parathyroid epithelial cells, and therefore the fat cell content is a valuable criterion in distinguishing between normal and abnormal. It is thought that stromal fat cells occupy about half of the normal parathyroid gland. Nevertheless, there is still controversy about the normal fat cell content in the normal parathyroid gland. The reported values for normal parathyroid fat content vary widely, from around 17% (Dekker et al., 1979; Dufour and Wilkerson, 1982) to 70% (Wells et al., 1980). Recent studies emphasize that the normal parathyroid gland has a much lower fat cell content than hitherto considered (Dekker et al., 1979; Dufour and Wilkerson, 1982; Saffos et al., 1984). In the present study, however, the mean stromal fat cell content was 38% which is close to the figure of 50% commonly accepted. Histopathologic determination of the distribution of fat cells and parenchymal cells in the parathyroid gland presents some problems. First, the two elements are variably distributed in the gland. Therefore, as reported by Grimelius and his associates (1978), examination of as many as 10 to 15 sections at different levels of the gland may be necessary to obtain a reliable ratio of parenchymal cells to fat cell tissue, although this is not achievable in a routine pathological examination. In this respect, the method used in this study is not sufficient to permit drawing a general conclusion about the stromal fat cell content in parathyroid glands. The results obtained here, however, are comparable to those reported by Dekker et al., (1979), Dufour et al., (1982), and Saffos et al., (1984). These authors used the largest section as
STROMAL FAT IN NORMAL PARATHYROID representative of the whole gland in estimating the parathyroid fat call content. Second,"normal" parathyroid glands are not easily obtainable for histologic examination. Parathyroid glands obtained at autopsy may not be normal, because various conditions at death influence the morphological features of the glands. For example, a slight decrease in renal function stimulates compensatory hyperfunction of the parathyroid gland even though laboratory data are within normal limits (Bricker et al., 1969). Therefore, as in this study, parathyroid glands resected at thyroid surgery from patients with normal parathyroid function provide a normal index of fat cell content in the glands. Taking these problems into account, our finding does not support the previous finding that the stromal fat cell content in a normal parathyroid gland is between 15% and 20% on average (Dekker et al., 1979, Dufour et al., 1982, and Saffos et al., 1984). In our study, the percentage of stromal fat cells was correlated with the age or the body constitution of the patient. Nevertheless, the range of the percentage of fat cells was quite wide among the glands in a given age or body constitution range. Furthermore, stromal adipose tissue was unevenly distributed and varied widely among the glands of each individual. Therefore, from the practical point of view, the determination of stromal fat cell content is not useful in discriminating between a normal and a hyperplastic parathyroid gland. As noted previously, decreased intracytoplasmic fat indicates abnormality in normal sized parathyroid glands (Roth and Gallagher 1976). References Bricker, N. S., E. Slatopolsky, E. Reiss and L. V. Avioli (1969). Calcium, phosphorus and bone in renal disease and transplantation. Arch. Intern. Med. 123, 543-553. Dekker, A., H. A. Dunsford and S. J. Geyer (1979). The normal parathyroid gland at autopsy: The significance of stromal fat in adult patients. J. Pathol. 128, 127-132. Dufour, D. R. and S. Y. Wilkerson (1982). The normal parathyroid revisited: Percentage of stromal fat. Hum. Pathol. 13, 717-721. Golden, A, and D. M. Kerwin (1982). The parathyroid glands, In : Endocrine Pathology, 2nd ed.(j. M. B. Bloodworth Jr. ed.), Williams and Wilkins, Baltimore, pp.205-220. L., G. Akerstrom, H. Johansson and H. Lundqvist (1978). Estimation of parenchymal cell content of human parathyroid glands using the image analyzing computer technique. Am. J. Pathol. 93, 793-800. Roth, S. I.(1971). Recent advances in parathyroid gland pathology. Am. J. Med, 50, 612-622. Roth, S. I. and M. J. Gallagher (1976). The rapid identification of normal parathyroid glands by the presence of intracellular Am. J. Pathol. 84, 521-528. fat. Saffos, R. O., R. M. Rhatigan and S. Urgulu (1984). The normal parathyroid and the borderline with early hyperplasia: A light microscopic study. Histopathology 8, 407-422. Straus, F. H. and E. Paloyan (1969). The pathology of hyperparathyroidism. Arch. Pathol. 73, 27-42. Wells, S. A. Jr., G. S. Leight and A. J. Ross (1980). Primary hyperparathyroidism. Curr. Probl. Surg. 17, 398-464.