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Parathyroid gland

Neoplasms

Parathyroid carcinoma


Reviewer: Monika Roychowdhury, M.D. (see Reviewers page)
Revised: 17 February 2013, last major update January 2013
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
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● Somewhat rare - accounts for less than 1% of all cases of primary hyperparathyroidism (J Cancer 2011;2:532)
● Usually detected because of palpable neck mass (75%), excessive PTH secretion, high serum calcium (> 14 mg/dl, may recur after surgery) and clinical effects of hypercalcemia (skeletal disease: 73%, renal disease: 26%), vocal cord paralysis
● Present in 15% with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, a rare autosomal disorder (Semin Oncol 2010;37:580)
● Equal male and female incidence
● Non-functioning tumors are rare (Am J Surg Pathol 1983;7:535)
● Rarely coexists with adenoma and hyperplasia (Arch Pathol Lab Med 1983;107:349)
● 1/3 recur locally; 1/3 have distant metastases
● 79% die of disease after multiple recurrences with repeated resections; 5 year survival 50% (Hum Pathol 2003;34:54)
● Types: chief cell (functional tumors that present with high serum calcium, 50% die of disease), oxyphil (rare, similar characteristics as chief cell carcinomas; higher Ki-67 and lower p27 than oxyphil adenomas, CK14- [usually expressed in oxyphil adenomas, Am J Surg Pathol 2002;26:344], abundant cytoplasmic mitochondria on EM)
● No current staging for parathyroid carcinomas exists

Diagnosis
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● Based on local invasion and metastases (clinical criteria, NOT microscopic criteria)
● Higher serum PTH and calcium levels than in parathyroid benign disease may be useful in diagnosis; PTH levels higher than 300 pg/ml are indicator of potential malignant disease (J Cancer 2011;2:532)

Prognostic factors
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● Macronucleoli, more than five mitoses per 50 high-power fields, and necrosis were associated with recurrent disease (Am J Surg Pathol 1993;17:820)

Case reports
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● 55 year old woman with pseudofollicular pattern (Mod Pathol 2000;13:210)

Treatment
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● Excise tumor, soft tissue and ipsilateral thyroid lobe
● Can excise isolated metastases
● Post-operative radiation to prevent local recurrence

Gross description
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● May be circumscribed
● Gray-white, firm, irregular, may exceed 10g, may adhere to adjacent structures, rarely within thyroid gland (Mod Pathol 1989;2:652)

Gross images
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Note large size and irregular cut surface


Cystic mass against thyroid lobe

Micro description
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● Uniform cells with minimal atypia in nodular or trabecular patterns with dense fibrous bands
● Tumor cells are spindled, mitotic figures are frequent, atypical mitotic figures relatively specific, capsular invasion present (tongue like protrusion of tumor cells through capsule) but usually NOT diagnostic because it may be due to prior hemorrhage
● Vascular invasion (81% had tumor inside vessel and attached to vessel wall), perineural invasion (19%) and soft tissue invasion usually reliable indicators of malignancy
● May produce amyloid
● Histologically, a definitive diagnosis of malignancy should be restricted to tumors displaying evidence of vascular invasion, capsular invasion with growth into adjacent tissues, or metastases; criteria for vascular and capsular invasion are similar to those used in thyroid pathology: vascular invasion should be observed in the capsule or in the surrounding soft tissues
● As criteria for malignancy are mostly architectural and require adequate sampling, frozen sections are of little value
● Diffuse nuclear enlargement with macronucleoli suggests malignancy (J Cancer 2011;2:532)
● May have pseudofollicular pattern (Mod Pathol 2000;13:210)

Micro images
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Nests of neoplastic cells that are not very pleomorphic


Pseudofollicular pattern resembling thyroid


Invasion of adjacent soft tissue and muscle


Figure 1: infiltrates skeletal muscle
Figure 2: mitotic activity
Figure 3: MIB-1
Figure 4: PTH


Cytology images
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Guided aspirate showing highly cellular smear with stippled nuclear chromatin and moderate pleomorphism

Positive stains
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● Higher Ki-67 (4-6% or more, Mod Pathol 1997;10:12, Hum Pathol 2003;34:54, Hum Pathol 1995;26:135)
● Lower p27kip1 than adenomas/hyperplasia (Am J Surg Pathol 1999;23:288)
● Cyclin D1 (90%, Mod Pathol 1999;12:412)
● PAS (intracellular glycogen)
● PTH

Negative stains
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● TTF

Molecular / cytogenetics description
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● Recently described in multiple endocrine neoplasia type 1 (MEN 1), although not a classic finding (Mayo Clin Proc 2002;77:866, Clin Endocrinol (Oxf) 2007;67:370)
● One case of parathyroid carcinoma has been reported in MEN2A syndrome (Clin Endocrinol (Oxf) 1997;47:747)

Pathogenesis:
● Five genes with a potential role in malignancy have been identified and studied (J Bone Miner Res 2008;23:1869)
  1) p53
  2) Breast carcinoma susceptibility (BRCA2)
  3) Cyclin D1/parathyroid adenomatosis gene 1 (PRAD1)
  4) Retinoblastoma tumor suppressor gene (RB)
  5) Hyperparathyroidism 2 tumor suppressor gene (HRPT2); has provided the best evidence

Differential diagnosis
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Follicular thyroid carcinoma: PTH negative (Am J Surg Pathol 1983;7:535)

End of Parathyroid gland > Neoplasms > Parathyroid carcinoma


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