Parathyroid gland
Neoplasms
Parathyroid carcinoma

Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Editor-in-Chief: Debra Zynger, M.D.
Mehmet Kefeli, M.D.

Topic Completed: 22 August 2019

Revised: 7 November 2019

Copyright: 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: Parathyroid carcinoma[TI] free full text[sb] pathology

Mehmet Kefeli, M.D.
Page views in 2018: 4,467
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Cite this page: Kefeli M. Parathyroid carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/parathyroidpthca.html. Accessed December 6th, 2019.
Definition / general
  • Malignant neoplasm originating from parathyroid parenchymal cells
Essential features
  • 90% of patients present with excess parathyroid hormone (PTH)
  • HRPT2 (CDC73) mutation strongly associated with familial and sporadic parathyroid carcinoma (> 70%)
  • One of the following features is necessary for definitive malignancy diagnosis of parathyroid lesion:
    • Vascular invasion
    • Perineural invasion
    • Invasion of adjacent structures / organs
    • Metastasis
  • Estimated 5 year and 10 year overall survival rates are 78 - 85% and 49 - 70%, respectively (Ann Surg Oncol 2015;22:3990)
Terminology
  • Parathyroid carcinoma
ICD coding
  • ICD-10: C75.0 – malignant neoplasm of parathyroid gland
Epidemiology
  • M = F
  • Mean age 56 years (range: 15 - 89 years)
  • Younger patients usually associated with familial syndromes
  • < 1% of cases of primary hyperparathyroidism (J Bone Miner Res 2008;23:1869)
Sites
Etiology
Clinical features
  • Palpable neck mass (30 - 75%)
  • Symptoms of overt hyperparathyroidism
    • Bone disease (osteitis fibrosa cystica, osteoporosis, fractures)
    • Renal disease (nephrolithiasis, nephrocalcinosis)
    • Neurocognitive symptoms (fatigue, weight loss, weakness, anxiety, depression, polyuria, polydipsia)
  • Jaw tumor (if associated with HPT-JT)
  • Neck pain
Diagnosis
  • One of the following microscopic features is necessary for definitive malignancy diagnosis of parathyroid lesion:
    • Vascular invasion
    • Perineural invasion
    • Invasion of adjacent structures / organs
    • Metastasis
Laboratory
Radiology description
Radiology images

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Xray lytic lesion

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Sestamibi scan

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Bone scan

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c-MIBI scintigraphy and CT

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Tc-MIBI SPECT/CT

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99mTc-MIBI SPECT/CT and MRI

Prognostic factors
  • The following microscopic features have been reported with aggressive growth in some parathyroid tumors (Am J Surg Pathol 1993;17:820):
    • Necrosis
    • Macronucleoli
    • > 5 mitoses per 50 high power
  • Older age at time of diagnosis, larger tumor size and male gender are negative prognostic factors (Ann Surg Oncol 2015;22:3990)
  • Estimated 5 year and 10 year overall survival rates are 78 - 85% and 49 - 70% respectively (Ann Surg Oncol 2015;22:3990)
Case reports
Treatment
Clinical images

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Intraoperative dissection

Gross description
Gross images

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Large size and irregular cut surface

Frozen section description
  • The distinction between parathyroid adenoma and carcinoma is often difficult to make on frozen section if the tumor does not show grossly evident invasion into adjacent structures
Microscopic (histologic) description
  • Nodular and solid growth pattern common
  • Broad fibrous bands can be present
  • Uniform cells or mild to moderate nuclear atypia
  • Mostly composed of chief cells; however, oxyphil cells and transitional cells can also be seen
  • Nuclear atypia, macronucleoli
  • Increased mitotic activity (> 5/50 HPF) and atypical mitosis may be seen
  • Necrosis can be present
  • One of the following features is necessary for definitive malignancy diagnosis of parathyroid lesion
    • Vascular invasion
    • Perineural invasion
    • Invasion of adjacent structures / organs
    • Metastasis
Microscopic (histologic) images

Contributed by Mehmet Kefeli, M.D.
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Solid and nodular growth

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Skeletal muscle invasion

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Uniform cytomorphology

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Numerous mitoses

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Prominent nucleoli


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PTH

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GATA3

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Thyroglobulin

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TTF1

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Ki-67

Virtual slides

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Parathyroid carcinoma

Cytology description
  • Cellular, composed of cohesive sheets, ribbon-like cords
  • Nuclei are uniform or show mild to moderate atypia
  • Coarsely granular chromatin pattern
  • Prominent nucleoli
  • Cytoplasm is moderately abundant and granular
  • Distinction between parathyroid carcinoma and adenoma is extremely difficult to make on cytology; nuclear pleomorphism, prominent macronucleoli, enlarged uniform hyperchromatic nuclei, mitotic figures favor carcinoma (Diagn Cytopathol 2016;44:688)
Cytology images

Contributed by Mehmet Kefeli, M.D.
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Cohesive clusters and sheets of cells

Positive stains
Negative stains
Molecular / cytogenetics description
Videos

Sample pathology report
  • Right neck, mass, excision:
    • Parathyroid carcinoma, oxyphilic type (see comment)
    • Comment: There is a cellular malignant tumor with thyroid gland and striated muscle invasion. Tumor cells characterized by eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin and prominent nucleoli. There are 12 mitoses per 50 high powered fields, some of which show atypical features. Lymphatic and vascular invasion are also seen. Immunohistochemically the tumor cells show strong expression of PTH, GATA3, chromogranin-A and synaptophysin while they are negative with thyroglobulin, TTF1, PAX-8, CEA, tyrosine hydroxylase. Ki-67 index is 16%. Morphological and immunohistochemical features strongly support parathyroid carcinoma, oxyphilic type. Complete nuclear parafibromin loss is detected, which correlates with HRPT2 (CDC73) mutation and also familial and sporadic parathyroid carcinoma.
Differential diagnosis
  • Parathyroid adenoma
    • Benign parathyroid neoplasm composed of chief cells, oncocytes or transitional oncocytes or an admixture of these cell types
    • Usually asymptomatic, no palpable mass and grossly smaller than parathyroid carcinoma
    • Serum calcium level elevated but often not as high as carcinoma
    • Scattered mitosis could be seen but high mitotic rate rare and usually lacks atypical mitosis
    • Lack of definitive diagnostic features of parathyroid carcinoma (invasion or metastases)
  • Atypical parathyroid adenoma
    • Rare type of adenoma which exhibits some of the features of parathyroid carcinoma such as cytological atypia, mitotic activity, fibrous bands, adherence to adjacent structures, trabecular growth pattern, tumor cells within the capsule
    • Lack of definitive diagnostic features of parathyroid carcinoma (invasion or metastases)
    • Ancillary immunohistochemical markers could be used for differential diagnosis of parathyroid adenoma and carcinoma (ki67, parafibromin, galectin3, PGP9.5, Rb, BCL2, P27, MDM2 and APC) (Endocr Pathol 2018;29:113)
  • Well differentiated thyroid carcinoma
    • Well differentiated thyroid malignancy arising from follicular epithelial cells
    • Papillary or follicular growth pattern, may have colloid, typical nuclear features for papillary carcinoma, lacks well defined cytoplasmic membrane
    • Positive for TTF1, thyroglobulin; negative for PTH, GATA3 (Endocr Pathol 2018;29:91), PAX8 expression can be overlapped between thyroid and parathyroid tumors and should not be considered as reliable marker for differential diagnosis
  • Poorly differentiated thyroid carcinoma
    • Follicular cell neoplasm that shows limited evidence of follicular differentiation
    • Solid, trabecular or insular growth pattern and lacks well defined cytoplasmic membrane
    • Positive for TTF1, thyroglobulin (reduced expression); negative for PTH, GATA3 (Endocr Pathol 2018;29:91)
  • Medullary thyroid carcinoma
  • Paraganglioma
  • Metastatic neuroendocrine tumors
Board review question #1

    Which of the following is diagnostic for parathyroid carcinoma in a parathyroid lesion?

  1. Tumor cells within the capsule
  2. Perineural invasion
  3. Increased mitotic activity (> 5/50 HPF)
  4. Broad fibrous bands
  5. Parafibromin loss
Board review answer #1
B. Perineural invasion of tumor cells is diagnostic of malignancy for parathyroid lesion

Reference: Parathyroid carcinoma

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Board review question #2
    Which of the following markers has diagnostic and prognostic role for parathyroid carcinoma?

  1. Isocitrate dehydrogenase 1 (IDH1)
  2. Menin
  3. Parafibromin
  4. SMARCB1/INI1
  5. Succinate dehydrogenase B (SDHB)
Board review answer #2
C. Parafibromin

Reference: Parathyroid carcinoma

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