Parathyroid >

Carcinoma

Definition

Rare malignant tumor with severe hypercalcemia invasion into surrounding tissues including thyroid, esophagus, vessels and soft tissues.

Clinical Features

  • Presentation:
    • typically hyperparathyroidism with skeletal and renal disease:1
      • suspect carcinoma if:
        • very high serum calcium or PTH
        • palpable cervical mass
        • vocal cord paralysis
        • recurrence of hyperparathyroidism short time after surgery2–5
    • sometimes parathyroid crisis6
    • rarely nonfunctioning:
      • said to be more aggressive7
      • may be caused by lack of conversion of pre-pro-PTH to biologically active compound8
  • May coexist with:

Gross Pathology

  • At operation, suspect carcinoma if tumor is:
    • hard
    • surrounded by a dense fibrous reaction
    • adherent to or infiltrating adjacent structures

Histopathology

  • Differs from adenoma mainly because of:
    • trabecular arrangement
    • dense fibrous bands (present in 90% of cases; Fig. 1
      Parathyroid carcinoma. Sharply outlined fibrous bands incompletely dividing the tumor into lobules.

      Fig. 1: Parathyroid carcinoma. Sharply outlined fibrous bands incompletely dividing the tumor into lobules.

      ):
      • some fibrous banding can also occur in:
        • adenoma
        • chief cell hyperplasia (particularly primary form)
    • spindle shape of tumor cells
    • mitotic figures (in 81%; Fig. 2
      Parathyroid carcinoma. Mitotic figures.

      Fig. 2: Parathyroid carcinoma. Mitotic figures.

      ):
      • note that occasional mitoses seen in:
        • 71% of adenomas
        • 80% of chief cell hyperplasias13
      • ensure mitoses are in tumor cells and not endothelial cells of the hyperplastic blood vessels that commonly accompany these tumors
    • capsular invasion (in 67%; Fig. 3
      Parathyroid carcinoma with capsular and possible capsular invasion.

      Fig. 3: Parathyroid carcinoma with capsular and possible capsular invasion.

      ):
      • may be nests of tumor cells within the capsule of a benign tumor
    • blood vessel invasion (in 12%)14,15
      • for tumor in a vein to be significant, it must be attached to the wall
  • Rarely composed of oxyphil cells16,17

Differential Diagnosis

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Parathyroid Adenoma and Hyperplasias

Prognosis

  • Overall relative survival:
    • 85.5% at 5 years
    • 49.1% at 10 years34
  • Ominous prognostic sign:
    • local recurrence within first 2 years after surgery
  • Tumor size and lymph node status not significant

References

1 Holmes EC, Morton DL, Ketcham AS. Parathyroid carcinoma. A collective review. Ann Surg. 1969;169:631–640.

2 Cohn K, Silverman M, Corrado J, Sedgewick C. Parathyroid carcinoma. The Lahey Clinic experience. Surgery. 1985;98:1095–1100.

3 Shane E, Bilezikian JP. Parathyroid carcinoma. A review of 62 patients. Endocr Rev. 1982;3:218–226.

4 Shortell CK, Andrus CH, Philips CE, Schwartz SI. Carcinoma of the parathyroid gland. A 30-year experience. Surgery. 1991;110:704–708.

5 Van Heerden JA, Weiland LH, ReMine H, Walls JT, Purnell DC. Cancer of the parathyroid glands. Arch Surg. 1979;114:475–480.

6 Palnaes Hansen C, Lau Pedersen M, Christensen L. Diagnosis, treatment and outcome of parathyroid cancer. A report of eight patients. Eur J Surg. 1991;157:517–520.

7 Aldinger KA, Hickey RC, Ibanez ML, Samaan NA. Parathyroid carcinoma. A clinical study of seven cases of functioning and two cases of nonfunctioning parathyroid cancer. Cancer. 1982;49:388–397.

8 Baba H, Kishihara M, Tohmon M, Fukase M, Kizaki T, Okada S, et al. Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism. J Clin Endocrinol Metab. 1986;62:247–252.

9 Dinnen JS, Greenwood RH, Jones JH, Walker DA, Williams ED. Parathyroid carcinoma in familial hyperparathyroidism. J Clin Pathol. 1977;30:966–975.

10 Haghighi P, Astarita RW, Wepsic T, Wolf PL. Concurrent primary parathyroid hyperplasia and parathyroid carcinoma. Arch Pathol Lab Med. 1983;107:349–350.

11 Streeten EA, Weinstein LS, Norton JA, Mulvihill JJ, White BJ, Friedman EM, et al. Studies in a kindred with parathyroid carcinoma. J Clin Endocrinol Metab. 1992;75:362–366.

12 Smith JF, Coombs RRH. Histological diagnosis of carcinoma of the parathyroid gland. J Clin Pathol. 1984;37:1370–1378.

13 Snover DC, Foucar K. Mitotic activity in benign parathyroid disease. Am J Clin Pathol. 1981;75:345–347.

14 Evans HL. Criteria for diagnosis of parathyroid carcinoma. A critical study. Surg Pathol. 1991;4:244–265.

15 Schantz A, Castleman B. Parathyroid carcinoma. Cancer. 1973;31:600–605.

16 Erickson LA, Jin L, Papotti M, Lloyd RV. Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases. Am J Surg Pathol. 2002;26:344–349.

17 Obara T, Fujimoto Y, Yamaguchi K, Takanashi R, Kino I, Sasaki Y. Parathyroid carcinoma of the oxyphil cell type. A report of two cases, light and electron microscopic study. Cancer. 1985;55:1482–1489.

18 Ordóñez NG, Ibañez ML, Samaan NA, Hickey RC. Immunoperoxidase study of uncommon parathyroid tumors. Report of two cases of nonfunctioning parathyroid carcinoma and one intrathyroid parathyroid tumor-producing amyloid. Am J Surg Pathol. 1983;7:535–542.

19 Boquist LL. Nucleolar organizer regions in normal, hyperplastic and neoplastic parathyroid glands. Virchows Arch [A]. 1990;417:237–241.

20 Kanematsu E, Matsui H, Deguchi T, Yamamoto O, Korematsu M, Kobayashi A, et al. Significance of AgNOR counts for distinguishing carcinoma from adenoma and hyperplasia in parathyroid gland. Hum Pathol. 1997;28:421–427.

21 Tuccari G, Abbona GC, Giuffre G, Papotti M, Gasparri G, Barresi G, et al. AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands. Virchows Archiv. 2000;437:298–303.

22 Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA, Lloyd RV. Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. Am J Surg Pathol. 1999;23:288–295.

23 Vargas MP, Vargas HI, Kleiner DE, Merino MJ. The role of prognostic markers (MiB-1, RB, and bcl-2) in the diagnosis of parathyroid tumors. Mod Pathol. 1997;10:12–17.

24 Vasef MA, Brynes RK, Sturm M, Bromley C, Robinson RA. Expression of cyclin D1 in parathyroid carcinomas, adenomas and hyperplasias: a paraffin immunohistochemical study. Mod Pathol. 1999;12:412–416.

25 Kytola S, Farnebo F, Obara T, Isola J, Grimelius L, Farnebo LO, et al. Patterns of chromosomal imbalances in parathyroid carcinomas. Am J Pathol. 2000;157:579–586.

26 Cryns VL, Thor A, Xu HJ, Hu SX, Wierman ME, Vickery AL, et al. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. 1994;330:757–761.

27 Szijan I, Orlow I, Dalamon V, Vergani P, Danilowicz K, Mezzadri N, et al. Alterations in the retinoblastoma pathway of cell cycle control in parathyroid tumors. Oncol Rep. 2000;7:421–425.

28 Bondeson L, Sandelin K, Grimelius L. Histopathological variables and DNA cytometry in parathyroid carcinoma. Am J Surg Pathol. 1993;17:820–829.

29 Harlow S, Roth SI, Bauer K, Marshall RB. Flow cytometric DNA analysis of normal and parathyroid glands. Mod Pathol. 1991;4:310–315.

30 Howard S, Anderson C, Diels W, Gerres K, Garcia B. Nuclear DNA density of parathyroid lesions. Pathol Res Pract. 1992;188:497–499.

31 Mallette L. DNA quantitation in the study of parathyroid lesions. A review. Am J Clin Pathol. 1992;98:305–311.

32 Obara T, Fujimoto Y, Hirayama A, Kanaji Y, Ito Y, Kodama T, et al. Flow cytometric DNA analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma. Cancer. 1990;65:1789–1793.

33 Shattuck TM, Välimäki S, Obara T, Gaz RD, Clark OH, Shoback D, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. 2003;349:1722–1729.

34 Hundahl SA, Fleming ID, Fremgen AM, Menck HR. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: a National Cancer Data Base report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. 1999;86:538–544.

Last updated: 4 Apr 2006

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