To the Editor.—We read with great interest the recent article by Drs Anton and Wheeler1 describing the role of frozen section in the evaluation of thyroid and parathyroid specimens, and we were pleased to see their emphasis on the use of preoperative fine needle aspiration and intraoperative cytologic preparations to guide the surgical management of these lesions. There are, however, a few points that we feel deserve further comment.The authors suggest that the distinction between a thyroid adenoma and an adenomatous nodule represents a pathologic diagnostic dilemma; however, in our opinion, this is misleading because both lesions are benign and will be managed similarly. Furthermore, the pathologic distinction between hyperplastic thyroid nodules, so-called adenomatous nodules, and thyroid adenomas has been shown in many cases to be unreliable as supported by the finding that, even in multinodular goiters, more than 60% of nodules are monoclonal proliferations.2With regard to the hyalinizing trabecular adenoma, the authors do not mention that a small subset of these tumors has been shown to have metastatic potential and hence the preferred term used by the World Health Organization, hyalinizing trabecular tumor. Molecular studies indicate that hyalinizing trabecular tumors share some of the molecular changes seen in papillary thyroid carcinomas such as the RET/PTC gene rearrangement, and thus these tumors may in fact represent an indolent variant of papillary carcinoma rather than a separate entity.3With respect to the parathyroid glands, we would stress that an experienced parathyroid (endocrine) surgeon very seldom needs to call for a frozen section to identify the tissue as parathyroid. At the Massachusetts General Hospital, the extent to which our 4 endocrine surgeons performing these operations use the frozen section for the purpose of identifying tissue as parathyroid is estimated to be less than 1% of cases, and usually only when there has been a previous thyroid or parathyroid operation. Frozen sections are predominantly used for distinguishing normal from abnormal glands (ie, to distinguish an adenoma or a double adenoma from primary chief cell hyperplasia).Although not mentioned by the authors, in our experience, the use of an intraoperative fat stain for evaluating intracellular and extracellular fat is helpful for distinguishing normal from abnormal parathyroid tissue. This is particularly true in children in whom stromal fat is sparse or absent or in very small biopsies in which the stromal fat is irregularly distributed. In fact, at our institution, frozen section examination of extremely small samples of normal parathyroid glands of less than 1 to 2 mm is easily done and very informative, especially in conjunction with use of a fat stain. In addition, our surgeons often apply the intraoperative parathyroid assay in conjunction with a single frozen section, and, in our hands, this has proven very successful.Finally, we would like to point out that the normal parathyroid glands do not technically contain water clear cells. Water clear cells have a specific ultrastructure, with a cytoplasm filled with enlarged vacuoles thought to represent abnormal secretory vesicles not found in the vacuolated chief cells of the normal gland.45 Water clear cells are only present in water clear hyperplasia and water clear adenomas, whereas the glycogen-rich chief cell is a normal variant of the chief cell secretory cycle.The authors have no relevant financial interest in the products or companies described in this letter.