Parathyroid >

Adenoma

Definition

A benign hypercellular neoplasm composed of chief cells, oncocytic cells, transitional oncocytic cells or a mixture of these cells types. Major cause of primary hyperparathyroidism.

Clinical Features

Gross Pathology

  • Typically parathyroids have normal or atrophic appearance:
  • Location:
    • ≈75% involve an inferior gland (Fig. 1
      Parathyroid adenoma arising from the left lower parathyroid gland.

      Fig. 1: Parathyroid adenoma arising from the left lower parathyroid gland.

      )
    • 15% involve a superior gland
    • 10% anomalous:
      • 70% in mediastinum
      • 20% within thyroid gland7
      • rest in soft tissues behind esophagus or rarely esophageal wall8,9
  • Usually oval
  • May show slight lobulation
  • Surrounded by thin connective tissue capsule
  • Cut section:
    • often grayish brown (Figs 2 and 3
      Gross appearance of parathyroid adenoma. Note the roundish shape, the homogeneous appearance interrupted by a few foci of fresh hemorrhagic or cystic changes, and the brown to yellowish color.

      Fig. 2: Gross appearance of parathyroid adenoma. Note the roundish shape, the homogeneous appearance interrupted by a few foci of fresh hemorrhagic or cystic changes, and the brown to yellowish color.

      Gross appearance of parathyroid adenoma. Note the roundish shape, the homogeneous appearance interrupted by a few foci of fresh hemorrhagic or cystic changes, and the brown to yellowish color.

      Fig. 3: Gross appearance of parathyroid adenoma. Note the roundish shape, the homogeneous appearance interrupted by a few foci of fresh hemorrhagic or cystic changes, and the brown to yellowish color.

      )
    • may be foci of:
      • hemorrhage
      • calcification
      • cystic change

Histopathology

  • Very cellular (Fig. 4
    Parathyroid adenoma. The tumor is hypercellular, homogeneous, and well vascularized.

    Fig. 4: Parathyroid adenoma. The tumor is hypercellular, homogeneous, and well vascularized.

    )
  • Rim of compressed non-neoplastic parathyroid tissue in ≈60% of cases
  • Cells:
    • usually chief cells predominate10
    • any of various cell types of normal parathyroid:
      • commonly combinations of:
        • chief cells
        • oxyphil cells
        • water-clear cells
        • transitional elements
  • Nuclei:
    • may be conspicuous variation in size
    • isolated or clustered huge hyperchromatic nuclei (Fig. 5
      Parathyroid adenoma with clusters of bizarre nuclei. This feature is not an indication of malignancy.

      Fig. 5: Parathyroid adenoma with clusters of bizarre nuclei. This feature is not an indication of malignancy.

      ):
      • do not indicate malignancy
      • more commonly seen in benign than in malignant tumors
    • sometimes an occasional mitosis
  • Pattern of growth:
    • generally diffuse
    • may be:
      • nesting
      • follicular (Fig. 6
        Parathyroid adenoma with follicular structures containing a colloid-like material simulating thyroid.

        Fig. 6: Parathyroid adenoma with follicular structures containing a colloid-like material simulating thyroid.

        ):
        • follicles may contain colloid-like material:
          • sometimes stains for amyloid, as in normal gland11
        • may simulate thyroid:
          • presence of birefringent crystals is clue for identifying thyroid
      • pseudopapillary12
  • Occasionally prominent clusters of mature lymphocytes:
    • scattered throughout the tumor
    • B and T cell type
    • sometimes admixed with plasma cells13 (Fig. 7
      Heavy lymphocytic infiltrate within a parathyroid adenoma.

      Fig. 7: Heavy lymphocytic infiltrate within a parathyroid adenoma.

      )
    • may be degenerative changes in tumor cells
    • important not to overdiagnose this as a lymphomatous infiltrate
    • may have autoimmune pathogenesis14,15
  • Ultrastructurally:
    • appearance of tumor cells:
      • indicative of hyperfunction
      • not substantially different from that in primary or secondary chief cell hyperplasia
      • main features (Fig. 8
        Electron micrograph of parathyroid adenoma. An oncocytic (oxyphilic) cell with numerous mitochondria (lower right) and chief cells with attached cisternae of rough endoplasmic reticulum and diffuse glycogen are illustrated. Dense-core endosecretory granules are primarily located in the ectoplasm. (×9300) (Courtesy of Dr Robert E. Erlandon, Memorial Sloan-Kettering Cancer Center)

        Fig. 8: Electron micrograph of parathyroid adenoma. An oncocytic (oxyphilic) cell with numerous mitochondria (lower right) and chief cells with attached cisternae of rough endoplasmic reticulum and diffuse glycogen are illustrated. Dense-core endosecretory granules are primarily located in the ectoplasm. (×9300) (Courtesy of Dr Robert E. Erlandon, Memorial Sloan-Kettering Cancer Center)

        ):
        • secretory granules
        • prominent Golgi apparatus
        • abundant cisternae of granular endoplasmic reticulum
        • annulate lamellae
        • numerous ribosomes
        • interdigitating cytoplasmic membranes16
    • in contrast to normal chief cells:
      • simultaneously:
        • large quantities of glycogen
        • secretory vacuoles

Special Stains and Immunohistochemistry

  • Reactivity for:
    • PTH:
      • intensity tends to be weaker in adenoma than in peripheral rim of normal gland17
    • various types of keratin18
  • Expression of:
    • neurofilament:
      • intermediate filament not found in normal parathyroid cells18
  • May be immunoreactivity for:
    • neuron-specific enolase
    • chromogranin
    • a number of peptide hormones
    • opioid peptides19–21

Differential Diagnosis

  • Chief cell hyperplasia:
    • a microscopically normal second gland is thought to represent best evidence that a parathyroid lesion is an adenoma rather than chief cell hyperplasia
    • overexpression of p53:
      • in a minority of parathyroid adenomas (as well as in carcinomas)
      • practically never in secondary hyperplasias32

Genetics

References

1 Nolan RB, Hayles AB, Woolner LB. Adenoma of the parathyroid gland in children. Report of case and brief review of the literature. Am J Dis Child. 1960;99:622–627.

2 Schachner SH, Hall A. Parathyroid adenoma and previous head-and-neck irradiation. Ann Intern Med. 1978;88:804.

3 Attie JN, Auguste LJ. Multiple parathyroid adenomas: Report of thirty-three cases. Surgery. 1990;108:1014–1019.

4 Verdonk CA, Edis AJ. Parathyroid “double adenomas. ” Fact or fiction? Surgery. 1981;90:523–526.

5 Woolner LB, Keating FR, Black BM. Tumors and hyperplasia of the parathyroid glands. A review of the pathological findings in 140 cases of primary hyperparathyroidism. Cancer. 1952;5:1069–1088.

6 Liechty RD, Teter A, Suba EJ. The tiny parathyroid adenoma. Surgery. 1986;100:1048–1052.

7 Pitsilos SA, Weber R, Baloch Z, LiVolsi A. Ectopic parathyroid adenoma initially suspected to be a thyroid lesion. Arch Pathol Lab Med. 2002;126:1541.

8 

Norris EH. Parathyroid adenoma. Study of 322 cases. Int Abstr Surg. 1947;84:1–41.
In Surg Gynecol Obstet. Jan. 1947;.

9 Sloane JA, Moody HC. Parathyroid adenoma in submucosa of esophagus. Arch Pathol Lab Med. 1978;102:242–243.

10 Carney JA. Pathology of hyperparathyroidism: A practical approach. Monogr Pathol. 1993;35:34–62.

11 Leedham PW, Pollock DJ. Intrafollicular amyloid in primary hyperparathyroidism. J Clin Pathol. 1970;23:811–818.

12 Ho K-J. Papillary parathyroid adenoma: A rare occurrence and its importance in differentiation from papillary carcinoma of the thyroid. Arch Pathol Lab Med. 1996;120:883–884.

13 Lawton TJ, Feldman M, LiVolsi V. Lymphocytic infiltrates in solitary parathyroid adenomas. Int J Surg Pathol. 1998;6:5–10.

14 Lam K-Y, Chan AC-L, Lo C-Y. Parathyroid adenomas with pronounced lymphocytic infiltration: No evidence of autoimmune pathogenesis. Endocrine Pathol. 2000;11:77–84.

15 Veress B, Nordenstrom J. Lymphocytic infiltration and destruction of parathyroid adenomas. A possible tumour- specific autoimmune reaction in two cases of primary hyperparathyroidism. Case reports. Histopathology. 1994;25:373–378.

16 Faccini JM. The ultrastructure of parathyroid glands removed from patients with primary hyperparathyroidism. A report of 40 cases, including four carcinomata. J Pathol. 1970;102:189–199.

17 Tomita T. Immunocytochemical staining patterns for parathyroid hormone and chromogranin in parathyroid hyperplasia, adenoma and carcinoma. Endocr Pathol. 1999;10:145–156.

18 Miettinen M, Clark R, Lehto V-P, Virtanen I, Damjanov I. Intermediate-filament proteins in parathyroid glands and parathyroid adenomas. Arch Pathol Lab Med. 1985;109:986–989.

19 Bostwick DG, Null WE, Holmes D, Weber E, Barchas JD, Bensch KG. Expression of opioid peptides in tumors. N Engl J Med. 1987;317:1439–1443.

20 Weber CJ, Marangos PJ, Richardson S, LoGerfo P, Hardy MA, Feind C, et al. Presence of neuron-specific enolase and somatostatin in human parathyroid tissues. Surgery. 1985;98:1008–1012.

21 Weiler R, Fischer-Colbrie R, Schmid KW, Feichtinger H, Bussolati G, Grimelius L, et al. Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors. Am J Surg Pathol. 1988;12:877–884.

22 Baloch ZW, LiVolsi VA. Oncocytic lesions of the neuroendocrine system. Semin Diagn Pathol. 1999;16:190–199.

23 Bedetti CD, Dekker A, Watson CG. Functioning oxyphil cell adenoma of the parathyroid gland. A clinicopathologic study of ten patients with hyperparathyroidism. Hum Pathol. 1984;15:1121–1126.

24 Ordoñez NG, Ibañez ML, Mackay B, Samaan NA, Hickey RC. Functioning oxyphil cell adenomas of parathyroid gland. Immunoperoxidase evidence of hormonal activity in oxyphil cells. Am J Clin Pathol. 1982;78:681–689.

25 Poole GV, Albertson DA, Marshall RB, Myers RT. Oxyphil cell adenoma and hyperparathyroidism. Surgery. 1982;92:799–805.

26 Woolpert HR, Vickery AL, Wang C-A. Functioning oxyphil cell adenomas of the parathyroid gland. A study of 15 cases. Am J Surg Pathol. 1989;13:500–504.

27 Legolvan DP, Moore BP, Nishiyama RH. Parathyroid hamartoma. Report of two cases and review of the literature. Am J Clin Pathol. 1977;67:31–35.

28 Straus FH, Kaplan EL, Nishiyama RH, Bigos ST. Five cases of parathyroid lipohyperplasia. Surgery. 1983;94:901–905.

29 Weiland LH, Garrison RC, ReMine WH, Scholz DA. Lipoadenoma of the parathyroid gland. Am J Surg Pathol. 1978;2:3–7.

30 Daroca PJ, Landau RL, Reed RJ, Kappelman MD. Functioning lipoadenoma of the parathyroid gland. Arch Pathol Lab Med. 1977;101:28–30.

31 Ducatman BS, Wilkerson SY, Brown JA. Functioning parathyroid lipoadenoma. Report of a case diagnosed by intraoperative touch preparations. Arch Pathol Lab Med. 1986;110:645–647.

32 Kishikawa S, Shan L, Ogihara K, Utsunomiya H, Nakamura M, Nakamura Y, et al. Overexpression and genetic abnormality of p53 in parathyroid adenomas. Pathol Int. 1999;49:853–857.

33 Heppner C, Kester MB, Agarwal SK, Debelenko LV, Emmert-Buck MR, Guru SC, et al. Somatic mutation of the MEN1 gene in parathyroid tumors. Nat Genet. 1997;16:375–378.

34 Shan L, Nakamura M, Nakamura Y, Yokoi T, Tsujimoto M, Arima R, et al. Somatic mutations of multiple endocrine neoplasia type 1 gene in the sporadic endocrine tumors. Lab Invest. 1998;78:471–475.

35 Kakudo K, Shan L. Recent advances in the molecular pathology of hyperparathyroidism. Endocr Pathol. 1999;10:3–14.

36 Stojadinovic A, Hoos A, Nissan A, Dudas M, Cordon-Cardo C, Shaha A, et al. Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis. Hum Pathol. 2003;34:54–64.

37 Koshiishi N, Chong JM, Fukasawa T, Ikeno R, Tanaka A, Kanazawa K, et al. Microsatellite instability and loss of heterozygosity in primary and secondary proliferative lesions of the parathyroid gland. Lab Invest. 1999;79:1051–1058.

38 Shan L, Nakamura M, Nakamura Y, Inoue D, Morimoto S, Yokoi T, et al. Comparative analysis of clonality and pathology in primary and secondary hyperparathyroidism. Virchows Arch. 1997;430:247–252.

39 Shan L, Yang Q, Nakamura Y, Nakamura M, Miyauchi A, Tsujimoto M, et al. Frequent loss of heterozygosity at 1p36.3 and p73 abnormality in parathyroid adenomas. Mod Pathol. 2001;14:273–278.

40 DeLellis RA, Tischler AS. Clonality of endocrine proliferative lesions: a critical reappraisal. Endocr Pathol. 1998;9:281–286.

41 Sanjuan X, Bryant BR, Sobel ME, Merino MJ. Clonality analysis of benign parathyroid lesions by human androgen receptor (HUMARA) gene assay. Endocr Pathol. 1998;9:293–300.

Last updated: 4 Apr 2006

Adenoma

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