Parathyroid Glands



Parathyroid Glands


James S. Lewis Jr.





  • I. NORMAL ANATOMY. The endodermally derived parathyroid glands develop from the third (inferior parathyroids) and fourth (superior parathyroids) pharyngeal pouches. They produce parathyroid hormone (PTH) which acts to increase serum calcium. They are normally found along the posterior surface of the thyroid gland, but given their complex embryologic development, normal variations in location range from within the substance of the thyroid gland, superiorly to the hyoid bone, inferiorly into the mediastinum, within the thymus gland, or within the pericardium. Furthermore, 2% to 7% of individuals have more than the usual four glands.

    Most normal parathyroid glands are from 0.3 to 0.6 cm in largest dimension, and the normal aggregate weight of all glands is 120 to 140 mg. They are brown to yellow-brown, oval, and have a thin capsule. Histologically, they consist of chief (or principal) cells and oxyphil cells. The former have round nuclei with granular chromatin and slightly eosinophilic to clear cytoplasm, and the latter have round nuclei and more abundant brightly eosinophilic and granular cytoplasm (e-Fig. 25.1).* Both types of cells are arranged in sheets, nests, and cords. Occasional pseudog-landular or pseudoacinar foci with central eosinophilic proteinaceous material can also be seen in the normal parathyroid. Oxyphil cells may also form small nodules in adults. Intraparenchymal adipose tissue is a normal feature of the parathyroid glands. It is usually scant in children but progressively increases with age to constitute about 50% of the gland by the fifth decade, and plateaus beyond that time (e-Fig. 25.2).

    Parathyroid cells, both chief and oxyphil, are positive by immunohistochemistry for PTH, chromogranin-A, and cytokeratins, and this immunoprofile is maintained in virtually all pathologic processes. Parathyroid cells are negative for thyroglobulin and thyroid transcription factor-1 (TTF-1).


  • II. GROSS EXAMINATION, TISSUE SAMPLING, AND HISTOLOGIC SLIDE PREPARATION



    • A. Fine needle aspiration. Fine needle aspiration of parathyroid lesions is rarely performed. The two exceptions are, first, when an adenoma arises within the substance of the parathyroid gland and thus a biopsy is taken as part of the evaluation of a presumed thyroid lesion, and second, when parathyroid carcinoma presents as a large neck mass.


    • B. Biopsy. Intraoperative biopsies (frozen sections) are frequently performed to confirm that the excised tissue is parathyroid because lymph nodes, thymus, thyroid, and fat may all be mistaken surgically for parathyroid tissue. The tissue should be weighed, but no other special handling is required.


    • C. Excision. The initial step in the gross examination of parathyroid glands is recording their weight and measurements in three dimensions. The glands should be closely examined and if firm, ragged, or irregular, should be inked around their periphery. They should then be sectioned and their color and consistency described. One section should be taken for histologic examination or, if the gland is 2 cm or larger, two to three sections should be taken.



  • III. DIAGNOSTIC FEATURES OF COMMON DISEASES



    • A. Nonneoplastic



      • 1. Abnormal development of the parathyroid glands sometimes occurs. The classic example is DiGeorge syndrome, in which there is failure in the development of several of the branchial pouches with resulting absence of the thymus and parathyroid glands. Neonates develop hypocalcemia due to lack of parathyroid hormone. Albright’s hereditary osteodystrophy is due to pseudohypoparathyroidism as a result of target organ unresponsiveness to PTH, and neonates present with hypocalcemia, hyperphosphatemia, and blunted responses to PTH.


      • 2. Parathyroiditis is a rare and poorly understood condition thought to be autoimmune in nature. It is characterized by extensive infiltration of the glands by lymphocytes. It is usually idiopathic and isolated but may be associated with a rare autoimmune polyglandular syndrome in which two or more endocrine glands are affected. Between one quarter and three quarters of patients will have circulating antiparathyroid tissue antibodies. Most patients have hypoparathyroidism, but parathyroiditis is sometimes associated with parathyroid hyperplasia. Histologically, the glands are infiltrated by clusters of lymphocytes, often with germinal center formation (e-Fig. 25.3). Plasma cells and fibrosis with clear parenchymal destruction are sometimes seen.


      • 3. Cysts of the parathyroid glands are relatively uncommon. They occur in the neck and less commonly in the mediastinum. Most patients do not have clinical hyperparathyroidism. Grossly, they are often loosely attached to the thyroid gland, range from microscopic up to as large as 10 cm, have thin walls, and contain watery fluid. Microscopically, they are lined by a cuboidal layer of parathyroid cells with round, hyperchromatic nuclei (e-Figs. 25.4 and 25.5). The cyst wall consists of fibrous tissue with entrapped islands of parathyroid chief cells.


      • 4. Hyperplasia is an increase in the overall mass of parathyroid cells and accounts for approximately 15% of all cases of primary hyperparathyroidism. Hyperplasia is divided into primary (where there is no known clinical stimulus), secondary (usually due to renal failure or another known metabolic cause), and tertiary (where there is an autonomously increased parathyroid mass in patients who have had secondary hyperparathyroidism and now are on dialysis or have had a renal transplant) (Table 25.1). A significant minority of cases of primary hyperparathyroidism (up to 40%) have been shown to have cells which are monoclonal, indicating that some cases represent true neoplasia. However, the clinical and pathophysiologic importance of this finding is unclear.

        Approximately 75% of patients are women, and 20% present with familial disease (most commonly multiple endocrine neoplasia [MEN] types 1 or 2A). Many patients are asymptomatic and are identified only indirectly through clinical evaluation for other reasons. The symptoms and signs of hyperparathyroidism can be vague such as fatigue, lethargy, nausea, constipation, arthralgia, or anorexia. The classic “bones, stones, and abdominal
        moans” (osteitis fibrosa cystica, kidney stones, and peptic ulcer disease) presentation is rare, and patients rarely present with a neck mass. Psychological disorders such as depression, psychosis, emotional instability, and confusion are sometimes the presenting symptoms. Patients frequently have osteopenia on clinical evaluation.








        TABLE 25.1 Classification of Parathyroid Hyperplasia












        Primary hyperparathyroidism


        No known stimulus


        Secondary hyperparathyroidism


        Known stimulus such as chronic renal failure, malabsorption, or vitamin D metabolism abnormality


        Tertiary hyperparathyroidism


        After longstanding renal failure with development of autonomous parathyroid hyperfunction


        In hyperplasia, all of the glands are involved but to varying degrees, leading to asymmetric findings. Grossly, the glands are usually enlarged and are soft and brown, but they may also be nodular or cystic. The total weight is above normal but is still usually <1 g. Microscopically, all of the glands show similar findings, but to different degrees, including increased parenchymal cells and a commensurate decrease in fat (e-Fig. 25.6). Both chief and oxyphil cells are usually increased, although chief cells usually predominate in a nodular, multinodular, or diffuse pattern. Sometimes a follicular (pseudog-landular) pattern is present. Cytologic atypia can be seen but is rarely widespread. There is minimal mitotic activity. A rare type of hyperplasia termed “water-clear cell hyperplasia” is sometimes encountered, in which all the cells have abundant, perfectly clear cytoplasm and no adipose tissue is present (e-Fig. 25.7).

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Oct 20, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Parathyroid Glands
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